Molecular Dysfunctions of Mitochondria-Associated Membranes (MAMs) in Alzheimer's Disease.

Alzheimer Disease/metabolism; Animals; Endoplasmic Reticulum/metabolism; Endoplasmic Reticulum Stress/physiology; Humans; Mitochondria/metabolism; Mitochondrial Membranes/metabolism; APOE; APP-C-terminal fragments (APP-CTFs); Alzheimer’s disease (AD); Amyloid β peptide (Aβ); Endoplasmic Reticulum (ER); Mitochondria-Associated Membranes (MAMs); Unfolded Protein Response (UPR); calcium signaling; cholesterol; fatty acid; lipids; mitochondria; phospholipids; tau; unfolded protein response; β amyloid precursor protein (APP)

Abstract :

[en] Alzheimer's disease (AD) is a multifactorial neurodegenerative pathology characterized by a progressive decline of cognitive functions. Alteration of various signaling cascades affecting distinct subcellular compartment functions and their communication likely contribute to AD progression. Among others, the alteration of the physical association between the endoplasmic reticulum (ER) and mitochondria, also reffered as mitochondria-associated membranes (MAMs), impacts various cellular housekeeping functions such as phospholipids-, glucose-, cholesterol-, and fatty-acid-metabolism, as well as calcium signaling, which are all altered in AD. Our review describes the physical and functional proteome crosstalk between the ER and mitochondria and highlights the contribution of distinct molecular components of MAMs to mitochondrial and ER dysfunctions in AD progression. We also discuss potential strategies targeting MAMs to improve mitochondria and ER functions in AD.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Eysert, Fanny

Kinoshita, Paula Fernanda

Mary, Arnaud ; Université Côte d'Azur, INSERM, CNRS, IPMC, France, Laboratory of excellence DistALZ, 660 route des Lucioles, 06560, Sophia-Antipolis, Valbonne, France.

Vaillant-Beuchot, Loan

Checler, Frédéric

Chami, Mounia

External co-authors :

yes

Language :

English

Title :

Molecular Dysfunctions of Mitochondria-Associated Membranes (MAMs) in Alzheimer's Disease.

Publication date :

2020

Journal title :

International Journal of Molecular Sciences

ISSN :

1422-0067

Publisher :

Multidisciplinary Digital Publishing Institute (MDPI), Switzerland

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBilu :

since 12 September 2023

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Bibliography

Checler, F. Processing of the beta-amyloid precursor protein and its regulation in Alzheimer’s disease. J. Neurochem. 1995, 65, 1431–1444.
Nhan, H.S.; Chiang, K.; Koo, E.H. The multifaceted nature of amyloid precursor protein and its proteolytic fragments: Friends and foes. Acta Neuropathol. 2015, 129, 1–19, doi:10.1007/s00401-014-1347-2.
Corder, E.H.; Saunders, A.M.; Strittmatter, W.J.; Schmechel, D.E.; Gaskell, P.C.; Small, G.W.; Roses, A.D.; Haines, J.L.; Pericak-Vance, M.A. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993, 261, 921–923, doi:10.1126/science.8346443.
Lambert, J.C.; Ibrahim-Verbaas, C.A.; Harold, D.; Naj, A.C.; Sims, R.; Bellenguez, C.; DeStafano, A.L.; Bis, J.C.; Beecham, G.W.; Grenier-Boley, B.; et al. Meta-Analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat. Genet. 2013, 45, 1452–1458, doi:10.1038/ng.2802.
Kunkle, B.W.; Grenier-Boley, B.; Sims, R.; Bis, J.C.; Damotte, V.; Naj, A.C.; Boland, A.; Vronskaya, M.; van der Lee, S.J.; Amlie-Wolf, A.; et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat. Genet. 2019, 51, 414–430, doi:10.1038/s41588-019-0358-2.
Bellenguez, C.; Grenier-Boley, B.; Lambert, J.C. Genetics of Alzheimer’s disease: Where we are, and where we are going. Curr. Opin. Neurobiol. 2020, 61, 40–48, doi:10.1016/j.conb.2019.11.024.
Tanzi, R.E.; Bertram, L. Twenty years of the Alzheimer’s disease amyloid hypothesis: A genetic perspective. Cell 2005, 120, 545–555, doi:10.1016/j.cell.2005.02.008.
Van Cauwenberghe, C.; Van Broeckhoven, C.; Sleegers, K. The genetic landscape of Alzheimer disease: Clinical implications and perspectives. Genet. Med. 2016, 18, 421–430, doi:10.1038/gim.2015.117.
Hardy, J.A.; Higgins, G.A. Alzheimer’s disease: The amyloid cascade hypothesis. Science 1992, 256, 184–185, doi:10.1126/science.1566067.
Panza, F.; Lozupone, M.; Logroscino, G.; Imbimbo, B.P. A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nat. Rev. Neurol. 2019, 15, 73–88, doi:10.1038/s41582-018-0116-6.
Flammang, B.; Pardossi-Piquard, R.; Sevalle, J.; Debayle, D.; Dabert-Gay, A.S.; Thévenet, A.; Lauritzen, I.; Checler, F. Evidence that the amyloid-β protein precursor intracellular domain, AICD, derives from β-secretase-generated C-terminal fragment. J. Alzheimer’s Dis. 2012, 30, 145–153, doi:10.3233/JAD-2012-112186.
Willem, M.; Tahirovic, S.; Busche, M.A.; Ovsepian, S.V.; Chafai, M.; Kootar, S.; Hornburg, D.; Evans, L.D.B.; Moore, S.; Daria, A.; et al. n-Secretase processing of APP inhibits neuronal activity in the hippocampus. Nature 2015, 526, 443–447, doi:10.1038/nature14864.
Zhang, Z.; Song, M.; Liu, X.; Su Kang, S.; Duong, D.M.; Seyfried, N.T.; Cao, X.; Cheng, L.; Sun, Y.E.; Ping Yu, S.; et al. Delta-secretase cleaves amyloid precursor protein and regulates the pathogenesis in Alzheimer’s disease. Nat. Commun. 2015, 6, 1–16, doi:10.1038/ncomms9762.
Baranger, K.; Marchalant, Y.; Bonnet, A.E.; Crouzin, N.; Carrete, A.; Paumier, J.M.; Py, N.A.; Bernard, A.; Bauer, C.; Charrat, E.; et al. MT5-MMP is a new pro-amyloidogenic proteinase that promotes amyloid pathology and cognitive decline in a transgenic mouse model of Alzheimer’s disease. Cell. Mol. Life Sci. 2016, 73, 217–236, doi:10.1007/s00018-015-1992-1.
Bourgeois, A.; Lauritzen, I.; Lorivel, T.; Bauer, C.; Checler, F.; Pardossi-Piquard, R. Intraneuronal accumulation of C99 contributes to synaptic alterations, apathy-like behavior, and spatial learning deficits in 3 × TgAD and 2 × TgAD mice. Neurobiol. Aging 2018, 71, 21–31, doi:10.1016/j.neurobiolaging.2018.06.038.
Lauritzen, I.; Pardossi-Piquard, R.; Bauer, C.; Brigham, E.; Abraham, J.D.; Ranaldi, S.; Fraser, P.; St-George-Hyslop, P.; Le Thuc, O.; Espin, V.; et al. The β-secretase-derived C-terminal fragment of βAPP, C99, but not Aβ, is a key contributor to early intraneuronal lesions in triple-transgenic mouse hippocampus. J. Neurosci. 2012, 32, 16243–16255, doi:10.1523/JNEUROSCI.2775-12.2012.
Lauritzen, I.; Pardossi-Piquard, R.; Bourgeois, A.; Pagnotta, S.; Biferi, M.G.; Barkats, M.; Lacor, P.; Klein, W.; Bauer, C.; Checler, F. Intraneuronal aggregation of the β-CTF fragment of APP (C99) induces Aβ-independent lysosomal-autophagic pathology. Acta Neuropathol. 2016, 132, 257–276.
Kwart, D.; Gregg, A.; Scheckel, C.; Murphy, E.A.; Paquet, D.; Duffield, M.; Fak, J.; Olsen, O.; Darnell, R.B.; Tessier-Lavigne, M. Erratum: A large panel of isogenic APP and PSEN1 mutant human iPSC neurons reveals shared endosomal abnormalities mediated by APP β-CTFs, not Aβ. Neuron 2019, 104, 256–270, doi:10.1016/j.neuron.2019.11.010.
Berridge, M.J. The endoplasmic reticulum: A multifunctional signaling organelle. Cell Calcium 2002, 32, 235–249, doi:10.1016/S0143416002001823.
Osellame, L.D.; Blacker, T.S.; Duchen, M.R. Cellular and molecular mechanisms of mitochondrial function. Best Pract. Res. Clin. Endocrinol. Metab. 2012, 26, 711–723, doi:10.1016/j.beem.2012.05.003.
Giacomello, M.; Pellegrini, L. The coming of age of the mitochondria—ER contact: A matter of thickness. 2016, 23, 1417–1427, doi:10.1038/cdd.2016.52.
Rizzuto, R.; Pinton, P.; Carrington, W.; Fay, F.S.; Fogarty, K.E.; Lifshitz, L.M.; Tuft, R.A.; Pozzan, T. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 1998, 280, 1763–1766, doi:10.1126/science.280.5370.1763.
Csordás, G.; Renken, C.; Várnai, P.; Walter, L.; Weaver, D.; Buttle, K.F.; Balla, T.; Mannella, C.A.; Hajnóczky, G. Structural and functional features and significance of the physical linkage between ER and mitochondria. J. Cell Biol. 2006, 174, 915–921, doi:10.1083/jcb.200604016.
Walter, L.; Hajnóczky, G. Mitochondria and endoplasmic reticulum: The lethal interorganelle cross-talk. J. Bioenerg. Biomembr. 2005, 37, 191–206.
Veeresh, P.; Kaur, H.; Sarmah, D.; Mounica, L.; Verma, G.; Kotian, V.; Kesharwani, R.; Kalia, K.; Borah, A.; Wang, X.; et al. Endoplasmic reticulum–mitochondria crosstalk: From junction to function across neurological disorders. Ann. N. Y. Acad. Sci. 2019, 1457, 41–60, doi:10.1111/nyas.14212.
van Vliet, A.R.; Agostinis, P. Mitochondria-Associated membranes and ER stress. In Current Topics in Microbiology and Immunology; Springer Nature Switzerland AG, 2018; Volume 414, pp. 73–102.
Gerakis, Y.; Hetz, C. Emerging roles of ER stress in the etiology and pathogenesis of Alzheimer’s disease. FEBS J. 2018, 285, 995–1011, doi:10.1111/febs.14332.
Hashimoto, S.; Saido, T.C. Critical review: Involvement of endoplasmic reticulum stress in the aetiology of Alzheimer’s disease. Open Biol. 2018, 8, doi:10.1098/rsob.180024.
Esteras, N.; Abramov, A.Y. Mitochondrial calcium deregulation in the mechanism of beta-amyloid and tau pathology. Cells 2020, 9, doi:10.3390/cells9092135.
Wang, W.; Zhao, F.; Ma, X.; Perry, G.; Zhu, X. Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: Recent advances. Mol. Neurodegener. 2020, 15, 1–22, doi:10.1186/s13024-020-00376-6.
Chen, H.; Chomyn, A.; Chan, D.C. Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J. Biol. Chem. 2005, 280, 26185–26192, doi:10.1074/jbc.M503062200.
Cipolat, S.; De Brito, O.M.; Dal Zilio, B.; Scorrano, L. OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc. Natl. Acad. Sci. USA 2004, 101, 15927–15932, doi:10.1073/pnas.0407043101.
Pich, S.; Bach, D.; Briones, P.; Liesa, M.; Camps, M.; Testar, X.; Palacín, M.; Zorzano, A. The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum. Mol. Genet. 2005, 14, 1405–1415, doi:10.1093/hmg/ddi149.
Youle, R.J.; Karbowski, M. Mitochondrial fission in apoptosis. Nat. Rev. Mol. Cell Biol. 2005, 6, 657–663, doi:10.1038/nrm1697.
Martorell-Riera, A.; Segarra-Mondejar, M.; Muñoz, J.P.; Ginet, V.; Olloquequi, J.; Pérez-Clausell, J.; Palacín, M.; Reina, M.; Puyal, J.; Zorzano, A.; et al. Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death. EMBO J. 2014, 33, 2388–2407, doi:10.15252/embj.201488327.
Tanaka, A.; Cleland, M.M.; Xu, S.; Narendra, D.P.; Suen, D.F.; Karbowski, M.; Youle, R.J. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J. Cell Biol. 2010, 191, 1367–1380, doi:10.1083/jcb.201007013.
Naon, D.; Zaninello, M.; Giacomello, M.; Varanita, T.; Grespi, F.; Lakshminaranayan, S.; Serafini, A.; Semenzato, M.; Herkenne, S.; Hernández-Alvarez, M.I.; et al. Critical reappraisal confirms that Mitofusin 2 is an endoplasmic reticulum-mitochondria tether. Proc. Natl. Acad. Sci. USA 2016, 113, 11249–11254, doi:10.1073/pnas.1606786113.
Chen, H.; McCaffery, J.M.; Chan, D.C. Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell 2007, 130, 548–562, doi:10.1016/j.cell.2007.06.026.
Zhang, L.; Trushin, S.; Christensen, T.A.; Bachmeier, B.V.; Gateno, B.; Schroeder, A.; Yao, J.; Itoh, K.; Sesaki, H.; Poon, W.W.; et al. Altered brain energetics induces mitochondrial fission arrest in Alzheimer’s Disease. Sci. Rep. 2016, 6, 1–12, doi:10.1038/srep18725.
Kim, Y.J.; Park, J.K.; Kang, W.S.; Kim, S.K.; Han, C.; Na, H.R.; Park, H.J.; Kim, J.W.; Kim, Y.Y.; Park, M.H.; et al. Association between mitofusin 2 gene polymorphisms and late-onset Alzheimer’s disease in the Korean population. Psychiatry Investig. 2017, 14, 81–85, doi:10.4306/pi.2017.14.1.81.
Wang, X.; Su, B.; Lee, H.G.; Li, X.; Perry, G.; Smith, M.A.; Zhu, X. Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J. Neurosci. 2009, 29, 9090–9103, doi:10.1523/JNEUROSCI.1357-09.2009.
Manczak, M.; Calkins, M.J.; Reddy, P.H. Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer’s disease: Implications for neuronal damage. Hum. Mol. Genet. 2011, 20, 2495–2509, doi:10.1093/hmg/ddr139.
Park, J.; Choi, H.; Min, J.S.; Kim, B.; Lee, S.R.; Yun, J.W.; Choi, M.S.; Chang, K.T.; Lee, D.S. Loss of mitofusin 2 links beta-amyloid-mediated mitochondrial fragmentation and Cdk5-induced oxidative stress in neuron cells. J. Neurochem. 2015, 132, 687–702, doi:10.1111/jnc.12984.
Gan, X.; Wu, L.; Huang, S.; Zhong, C.; Li, G.; Yu, H.; Swerdlow, R.H.; Chen, J.X.; Yan, S.S. Oxidative stress-mediated activation of extracellualr signal-regulated kinase contributes to mild cognitive impairment-related mitochondrial dysfuntion. Free Radic. Biol. Med. 2014, 75, 230–240, doi:10.1016/j.physbeh.2017.03.040.
Leal, N.S.; Schreiner, B.; Pinho, C.M.; Filadi, R.; Wiehager, B.; Karlström, H.; Pizzo, P.; Ankarcrona, M. Mitofusin-2 knockdown increases ER-mitochondria contact and decreases amyloid β-peptide production. J. Cell. Mol. Med. 2016, 20, 1686–1695, doi:10.1111/jcmm.12863.
Filadi, R.; Greotti, E.; Turacchio, G.; Luini, A.; Pozzan, T.; Pizzo, P. Presenilin 2 modulates endoplasmic reticulum-mitochondria coupling by tuning the antagonistic effect of mitofusin 2. Cell Rep. 2016, 15, 2226–2238, doi:10.1016/j.celrep.2016.05.013.
Berridge, M.J. Inositol triphosphate and calcium signalling. Nature 1993, 361, 315–325.
Joseph, S.K.; Hajnóczky, G. IP3 receptors in cell survival and apoptosis: Ca2+ release and beyond. Apoptosis 2007, 12, 951–968, doi:10.1007/s10495-007-0719-7.
Mikoshiba, K. IP3 receptor/Ca2+ channel: From discovery to new signaling concepts. J. Neurochem. 2007, 102, 1426–1446, doi:10.1111/j.1471-4159.2007.04825.x.
De Stefani, D.; Raffaello, A.; Teardo, E.; Szabò, I.; Rizzuto, R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 2011, 476, 336–340, doi:10.1038/nature10230.
Szabadkai, G.; Bianchi, K.; Várnai, P.; De Stefani, D.; Wieckowski, M.R.; Cavagna, D.; Nagy, A.I.; Balla, T.; Rizzuto, R. Chaperone-Mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J. Cell Biol. 2006, 175, 901–911, doi:10.1083/jcb.200608073.
Yoo, B.C.; Kim, S.H.; Cairns, N.; Fountoulakis, M.; Lubec, G. Deranged expression of molecular chaperones in brains of patients with Alzheimer’s disease. Biochem. Biophys. Res. Commun. 2001, 280, 249–258, doi:10.1006/bbrc.2000.4109.
Cuadrado-Tejedor, M.; Vilariño, M.; Cabodevilla, F.; Del Río, J.; Frechilla, D.; Pérez-Mediavilla, A. Enhanced expression of the voltage-dependent anion channel 1 (VDAC1) in Alzheimer’s disease transgenic mice: An insight into the pathogenic effects of amyloid-β. J. Alzheimers Dis. 2011, 23, 195–206, doi:10.3233/JAD-2010-100966.
Hedskog, L.; Pinho, C.M.; Filadi, R.; Rönnbäck, A.; Hertwig, L.; Wiehager, B.; Larssen, P.; Gellhaar, S.; Sandebring, A.; Westerlund, M.; et al. Modulation of the endoplasmic reticulum-mitochondria interface in Alzheimer’s disease and related models. Proc. Natl. Acad. Sci. USA 2013, 110, 7916–7921, doi:10.1073/pnas.1300677110.
Manczak, M.; Reddy, P.H. Abnormal interaction of VDAC1 with amyloid beta and phosphorylated tau causes mitochondrial dysfunction in Alzheimer’s disease. Hum. Mol. Genet. 2012, 21, 5131–5146, doi:10.1093/hmg/dds360.
Fernandez-Echevarria, C.; Díaz, M.; Ferrer, I.; Canerina-Amaro, A.; Marin, R. Aβ promotes VDAC1 channel dephosphorylation in neuronal lipid rafts. Relevance to the mechanisms of neurotoxicity in Alzheimer’s disease. Neuroscience 2014, 278, 354–366, doi:10.1016/j.neuroscience.2014.07.079.
Manczak, M.; Sheiko, T.; Craigen, W.J.; Reddy, P.H. Reduced VDAC1 protects against Alzheimer’s disease, mitochondria, and synaptic deficiencies. J. Alzheimer’s Dis. 2013, 37, 679–690, doi:10.3233/JAD-130761.
Ito, E.; Oka, K.; Etcheberrigaray, R.; Nelson, T.J.; McPhie, D.L.; Tofel-Grehl, B.; Gibson, G.E.; Alkon, D.L. Internal Ca2+ mobilization is altered in fibroblasts from patients with Alzheimer disease. Proc. Natl. Acad. Sci. USA 1994, 91, 534–538, doi:10.1073/pnas.91.2.534.
Cheung, K.; Mei, L.; Mak, D.D.; Hayashi, I.; Iwatsubo, T.; Kang, D.E.; Foskett, J.K. Gain-of-function enhancement of InsP3 receptor modal gating by familial Alzheimer’s disease-linked presenilin mutants in human cells and mouse neurons. Sci. Signal. 2010, 3, doi:10.1126/scisignal.2000818.Gain-of-function.
Demuro, A.; Parker, I. Cytotoxicity of intracellular Aβ42 amyloid oligomers involves Ca2+ release from the endoplasmic reticulum by stimulated production of inositol trisphosphate. J. Neurosci. 2013, 33, 3824–3833.
Shilling, D.; Müller, M.; Takano, H.; Mak, D.O.D.; Abel, T.; Coulter, D.A.; Foskett, J.K. Suppression of InsP3 receptor-mediated Ca2+ signaling alleviates mutant presenilin-linked familial Alzheimer’s disease pathogenesis. J. Neurosci. 2014, 34, 6910–6923, doi:10.1523/JNEUROSCI.5441-13.2014.
Cheung, K.H.; Shineman, D.; Müller, M.; Cárdenas, C.; Mei, L.; Yang, J.; Tomita, T.; Iwatsubo, T.; Lee, V.M.Y.; Foskett, J.K. Mechanism of Ca2+ disruption in Alzheimer’s disease by presenilin regulation of InsP3 receptor channel gating. Neuron 2008, 58, 871–883, doi:10.1016/j.neuron.2008.04.015.
Del Prete, D.; Checler, F.; Chami, M. Ryanodine receptors: physiological function and deregulation in Alzheimer disease. Mol. Neurodegener. 2014, 9, 21, doi:10.1186/1750-1326-9-21.
Lacampagne, A.; Liu, X.; Reiken, S.; Bussiere, R.; Meli, A.C.; Lauritzen, I.; Teich, A.F.; Zalk, R.; Saint, N.; Arancio, O.; et al. Post-Translational remodeling of ryanodine receptor induces calcium leak leading to Alzheimer’s disease-like pathologies and cognitive deficits. Acta Neuropathol. 2017, 134, 749–767, doi:10.1007/s00401-017-1733-7.
Bussiere, R.; Lacampagne, A.; Reiken, S.; Liu, X.; Scheuerman, V.; Zalk, R.; Martin, C.; Checler, F.; Marks, A.R.; Chami, M. Amyloid beta production is regulated by beta2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor. J. Biol. Chem. 2017, 292, 10153–10168, doi:10.1074/jbc.M116.743070.
Oules, B.; Del Prete, D.; Greco, B.; Zhang, X.; Lauritzen, I.; Sevalle, J.; Moreno, S.; Paterlini-Brechot, P.; Trebak, M.; Checler, F.; et al. Ryanodine receptor blockade reduces amyloid-beta load and memory impairments in Tg2576 mouse model of Alzheimer disease. J. Neurosci. 2012, 32, 11820–11834, doi:10.1523/JNEUROSCI.0875-12.2012.
Stutzmann, G.E.; Smith, I.; Caccamo, A.; Oddo, S.; LaFerla, F.M.; Parker, I. Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young, adult, and aged Alzheimer’s disease mice. J. Neurosci. 2006, 26, 5180–5189, doi:10.1523/JNEUROSCI.0739-06.2006.
Stutzmann, G.E.; Smith, I.; Caccamo, A.; Oddo, S.; Parker, I.; Laferla, F. Enhanced ryanodine-mediated calcium release in mutant PS1-expressing Alzheimer’s mouse models. Ann. N. Y. Acad. Sci. 2007, 1097, 265–277, doi:10.1196/annals.1379.025.
Li, C.; Li, L.; Yang, M.; Zeng, L.; Sun, L. PACS-2: A key regulator of mitochondria-associated membranes (MAMs). Pharmacol. Res. 2020, 160, 105080, doi:10.1016/j.phrs.2020.105080.
Werneburg, N.W.; Bronk, S.F.; Guicciardi, M.E.; Thomas, L.; Dikeakos, J.D.; Thomas, G.; Gores, G.J. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein-induced lysosomal translocation of proapoptotic effectors is mediated by phosphofurin acidic cluster sorting protein-2 (PACS-2). J. Biol. Chem. 2012, 287, 24427–24437, doi:10.1074/jbc.M112.342238.
Simmen, T.; Aslan, J.E.; Blagoveshchenskaya, A.D.; Thomas, L.; Wan, L.; Xiang, Y.; Feliciangeli, S.F.; Hung, C.-H.; Crump, C.M.; Thomas, G. PACS-2 controls endoplasmic reticulum-mitochondria communication and Bid-mediated apoptosis. EMBO J. 2005, 24, 717–729, doi:10.1038/sj.emboj.7600559.
Youker, R.T.; Shinde, U.; Day, R.; Thomas, G. At the crossroads of homoeostasis and disease: Roles of the PACS proteins in membrane traffic and apoptosis. Biochem. J. 2009, 421, 1–15, doi:10.1042/BJ20081016.
Stone, S.J.; Vance, J.E. Phosphatidylserine synthase-1 and-2 are localized to mitochondria-associated membranes. J. Biol. Chem. 2000, 275, 34534–34540, doi:10.1074/jbc.M002865200.
Iwasawa, R.; Mahul-Mellier, A.-L.; Datler, C.; Pazarentzos, E.; Grimm, S. Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction. EMBO J. 2011, 30, 556–568, doi:10.1038/emboj.2010.346.
Pagliuso, A.; Cossart, P.; Stavru, F. The ever-growing complexity of the mitochondrial fission machinery. Cell. Mol. Life Sci. 2018, 75, 355–374, doi:10.1007/s00018-017-2603-0.
Shen, Q.; Yamano, K.; Head, B.P.; Kawajiri, S.; Cheung, J.T.M.; Wang, C.; Cho, J.-H.; Hattori, N.; Youle, R.J.; van der Bliek, A.M. Mutations in Fis1 disrupt orderly disposal of defective mitochondria. Mol. Biol. Cell 2014, 25, 145–159, doi:10.1091/mbc.E13-09-0525.
Yu, R.; Jin, S.; Lendahl, U.; Nistér, M.; Zhao, J. Human Fis1 regulates mitochondrial dynamics through inhibition of the fusion machinery. EMBO J. 2019, 38, doi:10.15252/embj.201899748.
Rojansky, R.; Cha, M.-Y.; Chan, D.C. Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1. Elife 2016, 5, doi:10.7554/eLife.17896.
Namba, T. BAP31 regulates mitochondrial function via interaction with Tom40 within ER-mitochondria contact sites. Sci. Adv. 2019, 5, doi:10.1126/sciadv.aaw1386.
Joshi, A.U.; Saw, N.L.; Shamloo, M.; Mochly-Rosen, D. Drp1/Fis1 interaction mediates mitochondrial dysfunction, bioenergetic failure and cognitive decline in Alzheimer’s disease. Oncotarget 2017, 9, 6128–6143, doi:10.18632/oncotarget.23640.
Wang, T.; Chen, J.; Hou, Y.; Yu, Y.; Wang, B. BAP31 deficiency contributes to the formation of amyloid-β plaques in Alzheimer’s disease by reducing the stability of RTN3. FASEB J. 2019, 33, 4936–4946, doi:10.1096/fj.201801702R.
Manczak, M.; Reddy, P.H. Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated tau in Alzheimer’s disease neurons: Implications for mitochondrial dysfunction and neuronal damage. Hum. Mol. Genet. 2012, 21, 2538–2547, doi:10.1093/hmg/dds072.
Cho, D.-H.; Nakamura, T.; Fang, J.; Cieplak, P.; Godzik, A.; Gu, Z.; Lipton, S.A. S-Nitrosylation of Drp1 Mediates β-Amyloid-Related Mitochondrial Fission and Neuronal Injury. Science 2009, 324, 102–105.
De Vos, K.J.; Mórotz, G.M.; Stoica, R.; Tudor, E.L.; Lau, K.-F.; Ackerley, S.; Warley, A.; Shaw, C.E.; Miller, C.C.J. VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium homeostasis. Hum. Mol. Genet. 2012, 21, 1299–1311, doi:10.1093/hmg/ddr559.
Stoica, R.; Paillusson, S.; Gomez-Suaga, P.; Mitchell, J.C.; Lau, D.H.W.; Gray, E.H.; Sancho, R.M.; Vizcay-Barrena, G.; De Vos, K.J.; Shaw, C.E.; et al. ALS/FTD-associated FUS activates GSK-3β to disrupt the VAPB–PTPIP51 interaction and ER–mitochondria associations. EMBO Rep. 2016, 17, 1326–1342, doi:10.15252/embr.201541726.
Gomez-Suaga, P.; Paillusson, S.; Stoica, R.; Noble, W.; Hanger, D.P.; Miller, C.C.J. The ER-Mitochondria tethering complex VAPB-PTPIP51 regulates autophagy. Curr. Biol. 2017, 27, 371–385, doi:10.1016/j.cub.2016.12.038.
Galmes, R.; Houcine, A.; Vliet, A.R.; Agostinis, P.; Jackson, C.L.; Giordano, F. ORP5/ORP8 localize to endoplasmic reticulum–mitochondria contacts and are involved in mitochondrial function. EMBO Rep. 2016, 17, 800–810, doi:10.15252/embr.201541108.
Tokutake, Y.; Yamada, K.; Ohata, M.; Obayashi, Y.; Tsuchiya, M.; Yonekura, S. ALS-Linked P56S-VAPB mutation impairs the formation of multinuclear myotube in C2C12 Cells. Int. J. Mol. Sci. 2015, 16, 18628–18641, doi:10.3390/ijms160818628.
Stoica, R.; De Vos, K.J.; Paillusson, S.; Mueller, S.; Sancho, R.M.; Lau, K.-F.; Vizcay-Barrena, G.; Lin, W.-L.; Xu, Y.-F.; Lewis, J.; et al. ER-Mitochondria associations are regulated by the VAPB–PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nat. Commun. 2014, 5, doi:10.1038/ncomms4996.
Yamoah, A.; Tripathi, P.; Sechi, A.; Köhler, C.; Guo, H.; Chandrasekar, A.; Nolte, K.W.; Wruck, C.J.; Katona, I.; Anink, J.; et al. Aggregates of RNA binding proteins and ER chaperones linked to exosomes in granulovacuolar degeneration of the Alzheimer’s disease brain. J. Alzheimer’s Dis. JAD 2020, 139–156, doi:10.3233/JAD-190722.
Llorens-Marítin, M.; Jurado, J.; Hernández, F.; Ávila, J. GSK-3β, a pivotal kinase in Alzheimer disease. Front. Mol. Neurosci. 2014, 7, doi:10.3389/fnmol.2014.00046.
Lau, D.H.W.; Paillusson, S.; Hartopp, N.; Rupawala, H.; Mórotz, G.M.; Gomez-Suaga, P.; Greig, J.; Troakes, C.; Noble, W.; Miller, C.C.J. Disruption of endoplasmic reticulum-mitochondria tethering proteins in post-mortem Alzheimer’s disease brain. Neurobiol. Dis. 2020, 143, 105020, doi:10.1016/j.nbd.2020.105020.
Hayashi, T.; Su, T.P. σ-1 receptors (σ1 binding sites) form raft-like microdomains and target lipid droplets on the endoplasmic reticulum: Roles in endoplasmic reticulum lipid compartmentalization and export. J. Pharmacol. Exp. Ther. 2003, 306, 718–725, doi:10.1124/jpet.103.051284.
Watanabe, S.; Ilieva, H.; Tamada, H.; Nomura, H.; Komine, O.; Endo, F.; Jin, S.; Mancias, P.; Kiyama, H.; Yamanaka, K. Mitochondria-associated membrane collapse is a common pathomechanism in SIGMAR 1-and SOD 1-linked ALS. EMBO Mol. Med. 2016, 8, 1421–1437, doi:10.15252/emmm.201606403.
Hayashi, T.; Su, T.P. The potential role of sigma-1 receptors in lipid transport and lipid raft reconstitution in the brain: Implication for drug abuse. Life Sci. 2005, 77, 1612–1624, doi:10.1016/j.lfs.2005.05.009.
Gorbatyuk, M.; Gorbatyuk, O. The Molecular Chaperone GRP78/BiP as a Therapeutic Target for Neurodegenerative Disorders: A Mini Review. J. Genet. Syndr. Gene Ther. 2013, 4, doi:10.4172/2157-7412.1000128.
Prasad, M.; Pawlak, K.J.; Burak, W.E.; Perry, E.E.; Marshall, B.; Whittal, R.M.; Bose, H.S. Mitochondrial metabolic regulation by GRP78. Sci. Adv. 2017, 3, doi:10.1126/sciadv.1602038.
Hetz, C.; Papa, F.R. The unfolded protein response and cell fate control. Mol. Cell 2018, 69, 169–181, doi:10.1016/j.molcel.2017.06.017.
Hoozemans, J.J.M.; van Haastert, E.S.; Nijholt, D.A.T.; Rozemuller, A.J.M.; Scheper, W. Activation of the unfolded protein response is an early event in Alzheimer’s and Parkinson’s disease. Neurodegener. Dis. 2012, 10, 212–215, doi:10.1159/000334536.
Uddin, M.S.; Tewari, D.; Sharma, G.; Kabir, M.T.; Barreto, G.E.; Bin-Jumah, M.N.; Perveen, A.; Abdel-Daim, M.M.; Ashraf, G.M. Molecular mechanisms of ER stress and UPR in the pathogenesis of Alzheimer’s disease. Mol. Neurobiol. 2020, 57, 2902–2919, doi:10.1007/s12035-020-01929-y.
Katayama, T.; Imaizumi, K.; Sato, N.; Miyoshi, K.; Kudo, T.; Hitomi, J.; Morihara, T.; Yoneda, T.; Gomi, F.; Mori, Y.; et al. Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response. Nat. Cell Biol. 1999, 1, 479–485, doi:10.1038/70265.
Sadleir, K.R.; Popovic, J.; Vassar, R. ER stress is not elevated in the 5XFAD mouse model of Alzheimer’s disease. J. Biol. Chem. 2018, 293, 18434–18443, doi:10.1074/jbc.RA118.005769.
Hayashi, T.; Su, T.P. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca2+ signaling and cell survival. Cell 2007, 131, 596–610, doi:10.1016/j.cell.2007.08.036.
Hayashi, T.; Su, T.P. Regulating ankyrin dynamics: Roles of sigma-1 receptors. Proc. Natl. Acad. Sci. USA 2001, 98, 491–496, doi:10.1073/pnas.98.2.491.
Morin-Surun, M.P.; Collin, T.; Denavit-Saubie, M.; Baulieu, E.E.; Monnet, F.P. Intracellular σ1 receptor modulates phospholipase C and protein kinase C activities in the brainstem. Proc. Natl. Acad. Sci. USA 1999, 96, 8196–8199, doi:10.1073/pnas.96.14.8196.
Tsai, S.Y.; Hayashi, T.; Harvey, B.K.; Wang, Y.; Wu, W.W.; Shen, R.F.; Zhang, Y.; Becker, K.G.; Hoffer, B.J.; Su, T.P. Sigma-1 receptors regulate hippocampal dendritic spine formation via a free radical-sensitive mechanism involving Rac1·GTP pathway. Proc. Natl. Acad. Sci. USA 2009, 106, 22468–22473, doi:10.1073/pnas.0909089106.
Ryskamp, D.A.; Korban, S.; Zhemkov, V.; Kraskovskaya, N.; Bezprozvanny, I. Neuronal sigma-1 receptors: Signaling functions and protective roles in neurodegenerative diseases. Front. Neurosci. 2019, 13, 1–20, doi:10.3389/fnins.2019.00862.
Delprat, B.; Crouzier, L.; Su, T.-P.; Maurice, T. At the crossing of ER stress and MAMs: A key role of Sigma-1 receptor? Adv. Exp. Med. Biol. 2020, 1131, 699–718, doi:10.1007/978-3-030-12457-1_28.
Jansen, K.L.R.; Faull, R.L.M.; Storey, P.; Leslie, R.A. Loss of sigma binding sites in the CA1 area of the anterior hippocampus in Alzheimer’s disease correlates with CA1 pyramidal cell loss. Brain Res. 1993, 623, 299–302, doi:10.1016/0006-8993(93)91441-T.
Fehér, Á.; Juhász, A.; László, A.; Kálmán, J.; Pákáski, M.; Kálmán, J.; Janka, Z. Association between a variant of the sigma-1 receptor gene and Alzheimer’s disease. Neurosci. Lett. 2012, 517, 136–139, doi:10.1016/j.neulet.2012.04.046.
Huang, Y.; Zheng, L.; Halliday, G.; Dobson-Stone, C.; Wang, Y.; Tang, H.-D.; Cao, L.; Deng, Y.-L.; Wang, G.; Zhang, Y.-M.; et al. Genetic polymorphisms in Sigma-1 receptor and apolipoprotein E interact to influence the severity of Alzheimers disease. Curr. Alzheimer Res. 2011, 8, 765–770, doi:10.2174/156720511797633232.
Fisher, A.; Bezprozvanny, I.; Wu, L.; Ryskamp, D.A.; Bar-Ner, N.; Natan, N.; Brandeis, R.; Elkon, H.; Nahum, V.; Gershonov, E.; et al. AF710B, a Novel M1/sigma1 agonist with therapeutic efficacy in animal models of Alzheimer’s disease. Neurodegener. Dis. 2016, 16, 95–110, doi:10.1159/000440864.
Hall, H.; Iulita, M.F.; Gubert, P.; Flores Aguilar, L.; Ducatenzeiler, A.; Fisher, A.; Cuello, A.C. AF710B, an M1/sigma-1 receptor agonist with long-lasting disease-modifying properties in a transgenic rat model of Alzheimer’s disease. Alzheimers Dement. 2018, 14, 811–823, doi:10.1016/j.jalz.2017.11.009.
Maurice, T.; Strehaiano, M.; Duhr, F.; Chevallier, N. Amyloid toxicity is enhanced after pharmacological or genetic invalidation of the σ1 receptor. Behav. Brain Res. 2018, 339, 1–10, doi:10.1016/j.bbr.2017.11.010.
Lahmy, V.; Meunier, J.; Malmström, S.; Naert, G.; Givalois, L.; Kim, S.H.; Villard, V.; Vamvakides, A.; Maurice, T. Blockade of tau hyperphosphorylation and aβ 1-42 generation by the aminotetrahydrofuran derivative ANAVEX2-73, a mixed muscarinic and σ 1 receptor agonist, in a nontransgenic mouse model of Alzheimer’s disease. Neuropsychopharmacology 2013, 38, 1706–1723, doi:10.1038/npp.2013.70.
Lahmy, V.; Long, R.; Morin, D.; Villard, V.; Maurice, T. Mitochondrial protection by the mixed muscarinic/σ1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Aβ25–35 peptide-injected mice, a nontransgenic Alzheimer’s disease model. Front. Cell. Neurosci. 2015, 8, 1–11, doi:10.3389/fncel.2014.00463.
Tsai, S.Y.A.; Pokrass, M.J.; Klauer, N.R.; Nohara, H.; Su, T.P. Sigma-1 receptor regulates Tau phosphorylation and axon extension by shaping p35 turnover via myristic acid. Proc. Natl. Acad. Sci. USA 2015, 112, 6742–6747, doi:10.1073/pnas.1422001112.
Verfaillie, T.; Rubio, N.; Garg, A.D.; Bultynck, G.; Rizzuto, R.; Decuypere, J.P.; Piette, J.; Linehan, C.; Gupta, S.; Samali, A.; et al. PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death Differ. 2012, 19, 1880–1891, doi:cdd201274 [pii]10.1038/cdd.2012.74.
Munoz, J.P.; Ivanova, S.; Sanchez-Wandelmer, J.; Martinez-Cristobal, P.; Noguera, E.; Sancho, A.; Diaz-Ramos, A.; Hernandez-Alvarez, M.I.; Sebastian, D.; Mauvezin, C.; et al. Mfn2 modulates the UPR and mitochondrial function via repression of PERK. EMBO J. 2013, 32, 2348–2361, doi:10.1038/emboj.2013.168.
Toyofuku, T.; Okamoto, Y.; Ishikawa, T.; Sasawatari, S.; Kumanogoh, A. LRRK2 regulates endoplasmic reticulum-mitochondrial tethering through the PERK-mediated ubiquitination pathway. EMBO J. 2020, 39, e100875, doi:10.15252/embj.2018100875.
Hoozemans, J.J.; Veerhuis, R.; Van Haastert, E.S.; Rozemuller, J.M.; Baas, F.; Eikelenboom, P.; Scheper, W. The unfolded protein response is activated in Alzheimer’s disease. Acta Neuropathol. 2005, 110, 165–172.
Hoozemans, J.J.; van Haastert, E.S.; Nijholt, D.A.; Rozemuller, A.J.; Eikelenboom, P.; Scheper, W. The unfolded protein response is activated in pretangle neurons in Alzheimer’s disease hippocampus. Am. J. Pathol. 2009, 174, 1241–1251, doi:10.2353/ajpath.2009.080814.
Devi, L.; Ohno, M. PERK mediates eIF2alpha phosphorylation responsible for BACE1 elevation, CREB dysfunction and neurodegeneration in a mouse model of Alzheimer’s disease. Neurobiol. Aging 2014, 35, 2272–2281, doi:10.1016/j.neurobiolaging.2014.04.031.
Ma, T.; Trinh, M.A.; Wexler, A.J.; Bourbon, C.; Gatti, E.; Pierre, P.; Cavener, D.R.; Klann, E. Suppression of eIF2alpha kinases alleviates Alzheimer’s disease-related plasticity and memory deficits. Nat. Neurosci. 2013, 16, 1299–1305, doi:10.1038/nn.3486.
Page, G.; Rioux Bilan, A.; Ingrand, S.; Lafay-Chebassier, C.; Pain, S.; Perault Pochat, M.C.; Bouras, C.; Bayer, T.; Hugon, J. Activated double-stranded RNA-dependent protein kinase and neuronal death in models of Alzheimer’s disease. Neuroscience 2006, 139, 1343–1354, doi:10.1016/j.neuroscience.2006.01.047.
Abisambra, J.F.; Jinwal, U.K.; Blair, L.J.; O’Leary, J.C., 3rd.; Li, Q.; Brady, S.; Wang, L.; Guidi, C.E.; Zhang, B.; Nordhues, B.A.; et al. Tau accumulation activates the unfolded protein response by impairing endoplasmic reticulum-associated degradation. J. Neurosci. 2013, 33, 9498–9507, doi:10.1523/JNEUROSCI.5397-12.2013.
Radford, H.; Moreno, J.A.; Verity, N.; Halliday, M.; Mallucci, G.R. PERK inhibition prevents tau-mediated neurodegeneration in a mouse model of frontotemporal dementia. Acta Neuropathol. 2015, 130, 633–642, doi:10.1007/s00401-015-1487-z.
Segev, Y.; Barrera, I.; Ounallah-Saad, H.; Wibrand, K.; Sporild, I.; Livne, A.; Rosenberg, T.; David, O.; Mints, M.; Bramham, C.R.; et al. PKR inhibition rescues memory deficit and ATF4 overexpression in ApoE epsilon4 human replacement mice. J. Neurosci. 2015, 35, 12986–12993, doi:10.1523/JNEUROSCI.5241-14.2015.
O’Connor, T.; Sadleir, K.R.; Maus, E.; Velliquette, R.A.; Zhao, J.; Cole, S.L.; Eimer, W.A.; Hitt, B.; Bembinster, L.A.; Lammich, S.; et al. Phosphorylation of the translation initiation factor eIF2alpha increases BACE1 levels and promotes amyloidogenesis. Neuron 2008, 60, 988–1009, doi:10.1016/j.neuron.2008.10.047.
Yang, W.; Zhou, X.; Zimmermann, H.R.; Cavener, D.R.; Klann, E.; Ma, T. Repression of the eIF2alpha kinase PERK alleviates mGluR-LTD impairments in a mouse model of Alzheimer’s disease. Neurobiol. Aging 2016, 41, 19–24, doi:10.1016/j.neurobiolaging.2016.02.005.
Costa-Mattioli, M.; Gobert, D.; Stern, E.; Gamache, K.; Colina, R.; Cuello, C.; Sossin, W.; Kaufman, R.; Pelletier, J.; Rosenblum, K.; et al. eIF2alpha phosphorylation bidirectionally regulates the switch from short-to long-term synaptic plasticity and memory. Cell 2007, 129, 195–206, doi:10.1016/j.cell.2007.01.050.
Baleriola, J.; Walker, C.A.; Jean, Y.Y.; Crary, J.F.; Troy, C.M.; Nagy, P.L.; Hengst, U. Axonally synthesized ATF4 transmits a neurodegenerative signal across brain regions. Cell 2014, 158, 1159–1172, doi:10.1016/j.cell.2014.07.001.
DuBoff, B.; Götz, J.; Feany, M.B. Tau promotes neurodegeneration via DRP1 mislocalization In Vivo. Neuron 2012, 75, 618–632, doi:10.1016/j.neuron.2012.06.026.Tau.
Biswas, J.; Gupta, S.; Verma, D.K.; Gupta, P.; Singh, A.; Tiwari, S.; Goswami, P.; Sharma, S.; Singh, S. Involvement of glucose related energy crisis and endoplasmic reticulum stress: Insinuation of streptozotocin induced Alzheimer’s like pathology. Cell. Signal. 2018, 42, 211–226, doi:10.1016/j.cellsig.2017.10.018.
Cui, W.; Wang, S.; Wang, Z.; Wang, Z.; Sun, C.; Zhang, Y. Inhibition of PTEN attenuates endoplasmic reticulum stress and apoptosis via activation of PI3K/AKT pathway in Alzheimer’s disease. Neurochem. Res. 2017, 42, 3052–3060, doi:10.1007/s11064-017-2338-1.
Lin, L.; Liu, G.; Yang, L. Crocin improves cognitive behavior in rats with Alzheimer’s disease by regulating endoplasmic reticulum stress and apoptosis. Biomed. Res. Int. 2019, 2019, doi:10.1155/2019/9454913.
Reinhardt, S.; Schuck, F.; Grosgen, S.; Riemenschneider, M.; Hartmann, T.; Postina, R.; Grimm, M.; Endres, K. Unfolded protein response signaling by transcription factor XBP-1 regulates ADAM10 and is affected in Alzheimer’s disease. FASEB J. 2014, 28, 978–997, doi:10.1096/fj.13-234864.
Gerakis, Y.; Dunys, J.; Bauer, C.; Checler, F. Aβ42 oligomers modulate β-secretase through an XBP-1s-dependent pathway involving HRD1. Sci. Rep. 2016, 6, 37436, doi:10.1038/srep37436.
Bussiere, R.; Oules, B.; Mary, A.; Vaillant-Beuchot, L.; Martin, C.; El Manaa, W.; Vallee, D.; Duplan, E.; Paterlini-Brechot, P.; Alves Da Costa, C.; et al. Upregulation of the sarco-endoplasmic reticulum calcium ATPase 1 truncated isoform plays a pathogenic role in Alzheimer’s disease. Cells 2019, 8, doi:10.3390/cells8121539.
Mori, T.; Hayashi, T.; Hayashi, E.; Su, T.P. Sigma-1 receptor chaperone at the ER-Mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival. PLoS ONE 2013, 8, doi:10.1371/journal.pone.0076941.
Takeda, K.; Nagashima, S.; Shiiba, I.; Uda, A.; Tokuyama, T.; Ito, N.; Fukuda, T.; Matsushita, N.; Ishido, S.; Iwawaki, T.; et al. MITOL prevents ER stress-induced apoptosis by IRE1alpha ubiquitylation at ER-mitochondria contact sites. EMBO J. 2019, 38, e100999, doi:10.15252/embj.2018100999.
Son, S.M.; Byun, J.; Roh, S.E.; Kim, S.J.; Mook-Jung, I. Reduced IRE1alpha mediates apoptotic cell death by disrupting calcium homeostasis via the InsP3 receptor. Cell Death Dis. 2014, 5, e1188, doi:10.1038/cddis.2014.129.
Urano, F.; Wang, X.; Bertolotti, A.; Zhang, Y.; Chung, P.; Harding, H.P.; Ron, D. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 2000, 287, 664–666.
Nishitoh, H.; Matsuzawa, A.; Tobiume, K.; Saegusa, K.; Takeda, K.; Inoue, K.; Hori, S.; Kakizuka, A.; Ichijo, H. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 2002, 16, 1345–1355.
Lee, J.H.; Won, S.M.; Suh, J.; Son, S.J.; Moon, G.J.; Park, U.J.; Gwag, B.J. Induction of the unfolded protein response and cell death pathway in Alzheimer’s disease, but not in aged Tg2576 mice. Exp. Mol. Med. 2010, 42, 386–394, doi:10.3858/emm.2010.42.5.040.
Cissé, M.; Duplan, E.; Lorivel, T.; Dunys, J.; Bauer, C.; Meckler, X.; Gerakis, Y.; Lauritzen, I.; Checler, F. The transcription factor XBP1s restores hippocampal synaptic plasticity and memory by control of the Kalirin-7 pathway in Alzheimer model. Mol. Psychiatry 2017, 22, 1562–1575, doi:10.1038/mp.2016.152.
Casas-Tinto, S.; Zhang, Y.; Sanchez-Garcia, J.; Gomez-Velazquez, M.; Rincon-Limas, D.E.; Fernandez-Funez, P. The ER stress factor XBP1s prevents amyloid-beta neurotoxicity. Hum. Mol. Genet. 2011, 20, 2144–2160, doi:10.1093/hmg/ddr100.
Waldherr, S.M.; Strovas, T.J.; Vadset, T.A.; Liachko, N.F.; Kraemer, B.C. Constitutive XBP-1s-mediated activation of the endoplasmic reticulum unfolded protein response protects against pathological tau. Nat. Commun. 2019, 10, 4443, doi:10.1038/s41467-019-12070-3.
Acosta-Alvear, D.; Zhou, Y.; Blais, A.; Tsikitis, M.; Lents, N.H.; Arias, C.; Lennon, C.J.; Kluger, Y.; Dynlacht, B.D. XBP1 controls diverse cell type-and condition-specific transcriptional regulatory networks. Mol. Cell 2007, 27, 53–66, doi:10.1016/j.molcel.2007.06.011.
Chami, M.; Gozuacik, D.; Saigo, K.; Capiod, T.; Falson, P.; Lecoeur, H.; Urashima, T.; Beckmann, J.; Gougeon, M.L.; Claret, M.; et al. Hepatitis B virus-related insertional mutagenesis implicates SERCA1 gene in the control of apoptosis. Oncogene 2000, 19, 2877–2886.
Chami, M.; Gozuacik, D.; Lagorce, D.; Brini, M.; Falson, P.; Peaucellier, G.; Pinton, P.; Lecoeur, H.; Gougeon, M.L.; le Maire, M.; et al. SERCA1 truncated proteins unable to pump calcium reduce the endoplasmic reticulum calcium concentration and induce apoptosis. J. Cell Biol. 2001, 153, 1301–1314.
Chami, M.; Oules, B.; Szabadkai, G.; Tacine, R.; Rizzuto, R.; Paterlini-Brechot, P. Role of SERCA1 truncated isoform in the proapoptotic calcium transfer from ER to mitochondria during ER stress. Mol. Cell 2008, 32, 641–651, doi:10.1016/j.molcel.2008.11.014.
Xu, Q.; Bernardo, A.; Walker, D.; Kanegawa, T.; Mahley, R.W.; Huang, Y. Profile and regulation of apolipoprotein E (ApoE) expression in the CNS in mice with targeting of green fluorescent protein gene to the ApoE locus. J. Neurosci. 2006, 26, 4985–4994, doi:10.1523/JNEUROSCI.5476-05.2006.
Krasemann, S.; Madore, C.; Cialic, R.; Baufeld, C.; Calcagno, N.; El Fatimy, R.; Beckers, L.; O’Loughlin, E.; Xu, Y.; Fanek, Z.; et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 2017, 47, 566–581.e9, doi:10.1016/j.immuni.2017.08.008.
Mahley, R.W. Apolipoprotein E: Cholesterol transport protein with expanding role in cell biology. Science 1988, 240, 622–630, doi:10.1126/science.3283935.
Lane-Donovan, C.; Wong, W.M.; Durakoglugil, M.S.; Wasser, C.R.; Jiang, S.; Xian, X.; Herz, J. Genetic restoration of plasma apoe improves cognition and partially restores synaptic defects in ApoE-deficient mice. J. Neurosci. 2016, 36, 10141–10150, doi:10.1523/JNEUROSCI.1054-16.2016.
Neu, S.C.; Pa, J.; Kukull, W.; Beekly, D.; Kuzma, A.; Gangadharan, P.; Wang, L.-S.; Romero, K.; Arneric, S.P.; Redolfi, A.; et al. Apolipoprotein E genotype and sex risk factors for Alzheimer disease: A meta-analysis. JAMA Neurol. 2017, 74, 1178–1189, doi:10.1001/jamaneurol.2017.2188.
Mahley, R.W.; Huang, Y. Apolipoprotein E sets the stage: Response to injury triggers neuropathology. Neuron 2012, 76, 871–885, doi:10.1016/j.neuron.2012.11.020.
Castellano, J.M.; Kim, J.; Stewart, F.R.; Jiang, H.; DeMattos, R.B.; Patterson, B.W.; Fagan, A.M.; Morris, J.C.; Mawuenyega, K.G.; Cruchaga, C.; et al. Human apoE isoforms differentially regulate brain amyloid-β peptide clearance. Sci. Transl. Med. 2011, 3, doi:10.1126/scitranslmed.3002156.
Simonovitch, S.; Schmukler, E.; Masliah, E.; Pinkas-Kramarski, R.; Michaelson, D.M. The Effects of APOE4 on mitochondrial dynamics and proteins in vivo. J. Alzheimer’s Dis. 2019, 70, 861–875, doi:10.3233/JAD-190074.
Orr, A.L.; Kim, C.; Jimenez-Morales, D.; Newton, B.W.; Johnson, J.R.; Krogan, N.J.; Swaney, D.L.; Mahley, R.W. Neuronal apolipoprotein E4 expression results in proteome-wide alterations and compromises bioenergetic capacity by disrupting mitochondrial function. J. Alzheimer’s Dis. 2019, 68, 991–1011, doi:10.3233/JAD-181184.
Hayashi, T.; Rizzuto, R.; Hajnoczky, G.; Su, T.-P. MAM: More than just a housekeeper. Trends Cell Biol. 2009, 19, 81–88, doi:10.1016/j.tcb.2008.12.002.
Tambini, M.D.; Pera, M.; Kanter, E.; Yang, H.; Guardia-Laguarta, C.; Holtzman, D.; Sulzer, D.; Area-Gomez, E.; Schon, E.A. ApoE4 upregulates the activity of mitochondria-associated ER membranes. EMBO Rep. 2016, 17, 27–36, doi:10.15252/embr.201540614.
Oikawa, N.; Walter, J. Presenilins and γ-secretase in membrane proteostasis. Cells 2019, 8, 209, doi:10.3390/cells8030209.
Neely, K.M.; Green, K.N.; LaFerla, F.M. Presenilin is necessary for efficient proteolysis through the autophagy-lysosome system in a γ-secretase-independent manner. J. Neurosci. 2011, 31, 2781–2791, doi:10.1523/JNEUROSCI.5156-10.2010.
Száraz, P.; Bánhegyi, G.; Marcolongo, P.; Benedetti, A. Transient knockdown of presenilin-1 provokes endoplasmic reticulum stress related formation of autophagosomes in HepG2 cells. Arch. Biochem. Biophys. 2013, 538, 57–63, doi:10.1016/j.abb.2013.08.003.
Bezprozvanny, I.; Mattson, M.P. Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends Neurosci. 2008, 31, 454–463.
Tu, H.; Nelson, O.; Bezprozvanny, A.; Wang, Z.; Lee, S.F.; Hao, Y.H.; Serneels, L.; De Strooper, B.; Yu, G.; Bezprozvanny, I. Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer’s disease-linked mutations. Cell 2006, 126, 981–993, doi:10.1016/j.cell.2006.06.059.
Green, K.N.; Demuro, A.; Akbari, Y.; Hitt, B.D.; Smith, I.F.; Parker, I.; LaFerla, F.M. SERCA pump activity is physiologically regulated by presenilin and regulates amyloid β production. J. Cell Biol. 2008, 181, 1107–1116, doi:10.1083/jcb.200706171.
Stutzmann, G.E.; Caccamo, A.; LaFerla, F.M.; Parker, I. Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer’s-linked mutation in Presenilin1 results in exaggerated Ca2+ signals and altered membrane excitability. J. Neurosci. 2004, 24, 508–513, doi:10.1523/JNEUROSCI.4386-03.2004.
Area-Gomez, E.; De Groof, A.J.C.; Boldogh, I.; Bird, T.D.; Gibson, G.E.; Koehler, C.M.; Yu, W.H.; Duff, K.E.; Yaffe, M.P.; Pon, L.A.; et al. Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria. Am. J. Pathol. 2009, 175, 1810–1816, doi:10.2353/ajpath.2009.090219.
Zampese, E.; Fasolato, C.; Kipanyula, M.J.; Bortolozzi, M.; Pozzan, T.; Pizzo, P. Presenilin 2 modulates endoplasmic reticulum (ER)-mitochondria interactions and Ca2+ cross-talk. Proc. Natl. Acad. Sci. USA 2011, 108, 2777–2782, doi:10.1073/pnas.1100735108.
Kipanyula, M.J.; Contreras, L.; Zampese, E.; Lazzari, C.; Wong, A.K.C.; Pizzo, P.; Fasolato, C.; Pozzan, T. Ca 2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2. Aging Cell 2012, 11, 885–893, doi:10.1111/j.1474-9726.2012.00858.x.
Fedeli, C.; Filadi, R.; Rossi, A.; Mammucari, C.; Pizzo, P. PSEN2 (presenilin 2) mutants linked to familial Alzheimer disease impair autophagy by altering Ca2+ homeostasis. Autophagy 2019, 15, 2044–2062, doi:10.1080/15548627.2019.1596489.
Nelson, O.; Tu, H.; Lei, T.; Bentahir, M.; De Strooper, B.; Bezprozvanny, I. Familial Alzheimer disease-linked mutations specifically disrupt Ca 2+ leak function of presenilin 1. J. Clin. Invest. 2007, 117, 1230–1239, doi:10.1172/JCI30447.
Sepulveda-Falla, D.; Barrera-Ocampo, A.; Hagel, C.; Korwitz, A.; Vinueza-Veloz, M.F.; Zhou, K.; Schonewille, M.; Zhou, H.; Velazquez-Perez, L.; Rodriguez-Labrada, R.; et al. Familial Alzheimer’s disease-associated presenilin-1 alters cerebellar activity and calcium homeostasis. J. Clin. Investig. 2014, 124, 1552–1567, doi:10.1172/JCI66407.
Lee, J.H.; Yu, W.H.; Kumar, A.; Lee, S.; Mohan, P.S.; Peterhoff, C.M.; Wolfe, D.M.; Martinez-Vicente, M.; Massey, A.C.; Sovak, G.; et al. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 2010, 141, 1146–1158, doi:10.1016/j.cell.2010.05.008.
Müller, U.C.; Zheng, H. Physiological functions of APP family proteins. Cold Spring Harb. Perspect. Med. 2012, 2, 1–17, doi:10.1101/cshperspect.a006288.
Anandatheerthavarada, H.K.; Devi, L. Mitochondrial translocation of amyloid precursor protein and its cleaved products: Relevance to mitochondrial dysfunction in Alzheimer’s disease. Rev. Neurosci. 2007, 18, 343–354, doi:10.1515/revneuro.2007.18.5.343.
Anandatheerthavarada, H.K.; Biswas, G.; Robin, M.A.; Avadhani, N.G. Mitochondrial targeting and a novel transmembrane arrest of Alzheimer’s amyloid precursor protein impairs mitochondrial function in neuronal cells. J. Cell Biol. 2003, 161, 41–54, doi:10.1083/jcb.200207030.
Devi, L.; Prabhu, B.M.; Galati, D.F.; Avadhani, N.G.; Anandatheerthavarada, H.K. Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer’s disease brain is associated with mitochondrial dysfunction. J. Neurosci. 2006, 26, 9057–9068, doi:10.1523/JNEUROSCI.1469-06.2006.
Pagani, L.; Eckert, A. Amyloid-beta interaction with mitochondria. Int. J. Alzheimers. Dis. 2011, 2011, doi:10.4061/2011/925050.
Pavlov, P.F.; Wiehager, B.; Sakai, J.; Frykman, S.; Behbahani, H.; Winblad, B.; Ankarcrona, M. Mitochondrial γ-secretase participates in the metabolism of mitochondria-associated amyloid precursor protein. FASEB J. 2011, 25, 78–88, doi:10.1096/fj.10-157230.
Devi, L.; Ohno, M. Mitochondrial dysfunction and accumulation of the β-secretase-cleaved C-terminal fragment of APP in Alzheimer’s disease transgenic mice. Neurobiol. Dis. 2012, 45, 417–424.
Schreiner, B.; Hedskog, L.; Wiehager, B.; Ankarcrona, M. Amyloid-β peptides are generated in mitochondria-associated endoplasmic reticulum membranes. J. Alzheimer’s Dis. 2015, 43, 369–374, doi:10.3233/JAD-132543.
Pera, M.; Larrea, D.; Guardia-Laguarta, C.; Montesinos, J.; Velasco, K.R.; Agrawal, R.R.; Xu, Y.; Chan, R.B.; Di Paolo, G.; Mehler, M.F.; et al. Increased localization of APP-C99 in mitochondria-associated ER membranes causes mitochondrial dysfunction in Alzheimer disease. EMBO J. 2017, 36, 3356–3371, doi:10.15252/embj.201796797.
Del Prete, D.; Suski, J.M.; Oulès, B.; Debayle, D.; Gay, A.S.; Lacas-Gervais, S.; Bussiere, R.; Bauer, C.; Pinton, P.; Paterlini-Bréchot, P.; et al. Localization and processing of the amyloid-β protein precursor in mitochondria-associated membranes. J. Alzheimer’s Dis. 2017, 55, 1549–1570, doi:10.3233/JAD-160953.
Hansson, C.A.; Frykman, S.; Farmery, M.R.; Tjernberg, L.O.; Nilsberth, C.; Pursglove, S.E.; Ito, A.; Winblad, B.; Cowburn, R.F.; Thyberg, J.; et al. Nicastrin, presenilin, APH-1, and PEN-2 form active γ-secretase complexes in mitochondria. J. Biol. Chem. 2004, 279, 51654–51660, doi:10.1074/jbc.M404500200.
Ankarcrona, M.; Hultenby, K. Presenilin-1 is located in rat mitochondria. Biochem. Biophys. Res. Commun. 2002, 295, 766–770, doi:10.1016/S0006-291X(02)00735-0.
Area-Gomez, E.; Del Carmen Lara Castillo, M.; Tambini, M.D.; Guardia-Laguarta, C.; De Groof, A.J.C.; Madra, M.; Ikenouchi, J.; Umeda, M.; Bird, T.D.; Sturley, S.L.; et al. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. EMBO J. 2012, 31, 4106–4123, doi:10.1038/emboj.2012.202.
Marquer, C.; Devauges, V.; Cossec, J.C.; Liot, G.; Lécart, S.; Saudou, F.; Duyckaerts, C.; Lévêque-Fort, S.; Potier, M.C. Local cholesterol increase triggers amyloid precursor protein-Bace1 clustering in lipid rafts and rapid endocytosis. FASEB J. 2011, 25, 1295–1305, doi:10.1096/fj.10-168633.
Cordy, J.M.; Hussain, I.; Dingwall, C.; Hooper, N.M.; Turner, A.J. Exclusively targeting β-secretase to lipid rafts by GPI-anchor addition up-regulates β-site processing of the amyloid precursor protein. Proc. Natl. Acad. Sci. USA 2003, 100, 11735–11740.
Vetrivel, K.S.; Cheng, H.; Lin, W.; Sakurai, T.; Li, T.; Nukina, N.; Wong, P.C.; Xu, H.; Thinakaran, G. Association of γ-secretase with lipid rafts in post-golgi and endosome membranes. J. Biol. Chem. 2004, 279, 44945–44954, doi: 10.1074/jbc.M407986200
Hansson Petersen, C.A.; Alikhani, N.; Behbahani, H.; Wiehager, B.; Pavlov, P.F.; Alafuzoff, I.; Leinonen, V.; Ito, A.; Winblad, B.; Glaser, E.; et al. The amyloid-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc. Natl. Acad. Sci. USA 2008, 105, 13145–13150, doi: 10.1073/pnas.0806192105.
Vargas, T.; Ugalde, C.; Spuch, C.; Antequera, D.; Morán, M.J.; Martín, M.A.; Ferrer, I.; Bermejo-Pareja, F.; Carro, E. Aβ accumulation in choroid plexus is associated with mitochondrial-induced apoptosis. Neurobiol. Aging 2010, 31, 1569–1581, doi:10.1016/j.neurobiolaging.2008.08.017.
Bobba, A.; Amadoro, G.; Valenti, D.; Corsetti, V.; Lassandro, R.; Atlante, A. Mitochondrial respiratory chain Complexes I and IV are impaired by β-amyloid via direct interaction and through Complex I-dependent ROS production, respectively. Mitochondrion 2013, 13, 298–311, doi:10.1016/j.mito.2013.03.008.
Lin, M.T.; Beal, M.F. Alzheimer’s APP mangles mitochondria. Nat. Med. 2006, 12, 1241–1243.
Pavlov, P.F.; Petersen, C.H.; Glaser, E.; Ankarcrona, M. Mitochondrial accumulation of APP and Aβ: Significance for Alzheimer disease pathogenesis. J. Cell. Mol. Med. 2009, 13, 4137–4145, doi:10.1111/j.1582-4934.2009.00892.x.
Agrawal, R.R.; Montesinos, J.; Larrea, D.; Area-Gomez, E.; Pera, M. The silence of the fats: A MAM’s story about Alzheimer. Neurobiol. Dis. 2020, 145, 105062, doi:10.1016/j.nbd.2020.105062.
Kogot-Levin, A.; Saada, A. Ceramide and the mitochondrial respiratory chain. Biochimie 2014, 100, 88–94, doi:10.1016/j.biochi.2013.07.027.
Montesinos, J.; Pera, M.; Larrea, D.; Guardia-Laguarta, C.; Agrawal, R.R.; Velasco, K.R.; Yun, T.D.; Stavrovskaya, I.G.; Xu, Y.; Koo, S.Y.; et al. The Alzheimer’s disease-associated C99 fragment of APP regulates cellular cholesterol trafficking. EMBO J. 2020, 39, doi:10.15252/embj.2019103791.
Vaillant-Beuchot, L.; Mary, A.; Pardossi-Piquard, R.; Bourgeois, A.; Lauritzen, I.; Eysert, F.; Kinoshita, P.F.; Cazareth, J.; Badot, C.; Fragaki, K.; et al. Accumulation of amyloid precursor protein C-terminal fragments triggers mitochondrial structure, function, and mitophagy defects in Alzheimer’s disease models and human brains. Acta Neuropathol. 2020, doi:10.1007/s00401-020-02234-7.
Ittner, L.M.; Ke, Y.D.; Delerue, F.; Bi, M.; Gladbach, A.; van Eersel, J.; Wölfing, H.; Chieng, B.C.; Christie, M.J.; Napier, I.A.; et al. Dendritic function of tau mediates amyloid-β toxicity in alzheimer’s disease mouse models. Cell 2010, 142, 387–397, doi:10.1016/j.cell.2010.06.036.
Arendt, T.; Stieler, J.T.; Holzer, M. Tau and tauopathies. Brain Res. Bull. 2016, 126, 238–292, doi:10.1016/j.brainresbull.2016.08.018.
Roy, S.; Zhang, B.; Lee, V.M.Y.; Trojanowski, J.Q. Axonal transport defects: A common theme in neurodegenerative diseases. Acta Neuropathol. 2005, 109, 5–13, doi:10.1007/s00401-004-0952-x.
David, D.C.; Hauptmann, S.; Scherping, I.; Schuessel, K.; Keil, U.; Rizzu, P.; Ravid, R.; Dröse, S.; Brandt, U.; Müller, W.E.; et al. Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice. J. Biol. Chem. 2005, 280, 23802–23814, doi:10.1074/jbc.M500356200.
Cummins, N.; Tweedie, A.; Zuryn, S.; Bertran-Gonzalez, J.; Götz, J. Disease-associated tau impairs mitophagy by inhibiting Parkin translocation to mitochondria. EMBO J. 2019, 38, doi:10.15252/embj.201899360.
Li, X.C.; Hu, Y.; Wang, Z.H.; Luo, Y.; Zhang, Y.; Liu, X.P.; Feng, Q.; Wang, Q.; Ye, K.; Liu, G.P.; et al. Human wild-type full-length tau accumulation disrupts mitochondrial dynamics and the functions via increasing mitofusins. Sci. Rep. 2016, 6, 1–10, doi:10.1038/srep24756.
Perreault, S.; Bousquet, O.; Lauzon, M.; Paiement, J.; Leclerc, N. Increased association between rough endoplasmic reticulum membranes and mitochondria in transgenic mice that express P301L Tau. J. Neuropathol. Exp. Neurol. 2009, 68, 503–514, doi: 10.1097/NEN.0b013e3181a1fc49
Ebneth, A.; Godemann, R.; Stamer, K.; Illenberger, S.; Trinczek, B.; Mandelkow, E.-M.; Mandelkow, E. Overexpression of Tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: Implications for Alzheimer’s disease. J. Cell Biol. 1998, 143, 777–794, doi: 10.1083/jcb.143.3.777
Afreen, S.; Riherd Methner, D.N.; Ferreira, A. Tau45-230 association with the cytoskeleton and membrane-bound organelles: Functional implications in neurodegeneration. Neuroscience 2017, 362, 104–117, doi:10.1016/j.neuroscience.2017.08.026.
Yoshiyama, Y.; Higuchi, M.; Zhang, B.; Huang, S.M.; Iwata, N.; Saido, T.C.C.; Maeda, J.; Suhara, T.; Trojanowski, J.Q.; Lee, V.M.Y. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 2007, 53, 337–351, doi:10.1016/j.neuron.2007.01.010.
Gong, T.; Wang, Q.; Lin, Z.; Chen, M.L.; Sun, G.Z. Endoplasmic reticulum (ER) stress inhibitor salubrinal protects against ceramide-induced SH-SY5Y cell death. Biochem. Biophys. Res. Commun. 2012, 427, 461–465, doi:10.1016/j.bbrc.2012.08.068.
Lee, D.Y.; Lee, K.S.; Lee, H.J.; Kim, D.H.; Noh, Y.H.; Yu, K.; Jung, H.Y.; Lee, S.H.; Lee, J.Y.; Youn, Y.C.; et al. Activation of PERK signaling attenuates Aβ-mediated ER stress. PLoS ONE 2010, 5, e10489, doi:10.1371/journal.pone.0010489.
Huang, X.; Chen, Y.; Zhang, H.; Ma, Q.; Zhang, Y.; Xu, H. Salubrinal attenuates β-amyloid-induced neuronal death and microglial activation by inhibition of the NF-κB pathway. Neurobiol. Aging 2012, 33, 1007.e9–1007.e17, doi:10.1016/j.neurobiolaging.2011.10.007.
Barreda-Manso, M.A.; Yanguas-Casás, N.; Nieto-Sampedro, M.; Romero-Ramírez, L. Salubrinal inhibits the expression of proteoglycans and favors neurite outgrowth from cortical neurons in vitro. Exp. Cell Res. 2015, 335, 82–90, doi:10.1016/j.yexcr.2015.04.002.
Paris, D.; Ganey, N.J.; Laporte, V.; Patel, N.S.; Beaulieu-Abdelahad, D.; Bachmeier, C.; March, A.; Ait-Ghezala, G.; Mullan, M.J. Reduction of β-amyloid pathology by celastrol in a transgenic mouse model of Alzheimer’s disease. J. Neuroinflamm. 2010, 7, 1–15, doi:10.1186/1742-2094-7-17.
Ho, S.W.; Tsui, Y.T.C.; Wong, T.T.; Cheung, S.K.K.; Goggins, W.B.; Yi, L.M.; Cheng, K.K.; Baum, L. Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in transgenic mouse models of frontotemporal lobar degeneration and Alzheimer’s disease. Transl. Neurodegener. 2013, 2, 1–9, doi:10.1186/2047-9158-2-24.
Twaroski, Y.; Zaja, C.; Bosnjak, B. Altered Mitochondrial dynamics contributes to propofol-induced cell death in human stem cell-derived neurons. Physiol. Behav. 2015, 123, 1067–1083, doi:10.1016/j.physbeh.2017.03.040.
Xie, N.; Wang, C.; Lian, Y.; Wu, C.; Zhang, H.; Zhang, Q. Inhibition of mitochondrial fission attenuates Aβ-induced microglia apoptosis. Neuroscience 2014, 256, 36–42, doi:10.1016/j.neuroscience.2013.10.011.
Reddy, P.H.; Manczak, M.; Yin, X. Mitochondria-Division inhibitor 1 protects against amyloid-β induced mitochondrial fragmentation and synaptic damage in Alzheimer’s disease. J. Alzheimer’s Dis. 2017, 58, 147–162, doi:10.3233/JAD-170051.
Yeon, J.Y.; Min, S.H.; Park, H.J.; Kim, J.W.; Lee, Y.H.; Park, S.Y.; Jeong, P.S.; Park, H.; Lee, D.S.; Kim, S.U.; et al. Mdivi-1, mitochondrial fission inhibitor, impairs developmental competence and mitochondrial function of embryos and cells in pigs. J. Reprod. Dev. 2015, 61, 81–89, doi:10.1262/jrd.2014-070.
Guo, X.; Disatnik, M.; Monbureau, M.; Shamloo, M.; Mochly-rosen, D.; Qi, X. Inhibition of mitochondrial fragmentation diminishes Huntington’s disease-associated neurodegeneration. J. Clin. Investig. 2013, 123, 5371–5388, doi:10.1172/JCI70911DS1.
Arismendi-Morillo, G.; Castellano-Ramírez, A.; Seyfried, T.N. Ultrastructural characterization of the Mitochondria-associated membranes abnormalities in human astrocytomas: Functional and therapeutics implications. Ultrastruct. Pathol. 2017, 41, 234–244, doi:10.1080/01913123.2017.1300618.
Lynes, E.M.; Bui, M.; Yap, M.C.; Benson, M.D.; Schneider, B.; Ellgaard, L.; Berthiaume, L.G.; Simmen, T. Palmitoylated TMX and calnexin target to the mitochondria-associated membrane. EMBO J. 2012, 31, 457–470, doi:10.1038/emboj.2011.384.
Garrido-Maraver, J.; Loh, S.H.Y.; Martins, L.M. Forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a Drosophila model of Alzheimer’s disease. Biol. Open 2020, 9, doi:10.1242/bio.047530.
Csordás, G.; Várnai, P.; Golenár, T.; Roy, S.; Purkins, G.; Schneider, T.G.; Balla, T.; Hajnóczky, G. Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface. Mol. Cell 2010, 39, 121–132, doi:10.1016/j.molcel.2010.06.029.
Lee, H.J.; Jung, Y.H.; Choi, G.E.; Kim, J.S.; Chae, C.W.; Lim, J.R.; Kim, S.Y.; Yoon, J.H.; Cho, J.H.; Lee, S.J.; et al. Urolithin A suppresses high glucose-induced neuronal amyloidogenesis by modulating TGM2-dependent ER-mitochondria contacts and calcium homeostasis. Cell Death Differ. 2020, doi:10.1038/s41418-020-0593-1.