Anti-inflammatory actions of peroxisome proliferator-activated receptor gamma agonists in Alzheimer's disease.

Anti-Inflammatory Agents, Non-Steroidal; Receptors, Cytoplasmic and Nuclear; Transcription Factors; Alzheimer Disease/pathology; Alzheimer Disease/prevention & control; Animals; Anti-Inflammatory Agents, Non-Steroidal/pharmacology; Humans; Inflammation/prevention & control; Receptors, Cytoplasmic and Nuclear/agonists; Receptors, Cytoplasmic and Nuclear/biosynthesis; Receptors, Cytoplasmic and Nuclear/physiology; Transcription Factors/agonists; Transcription Factors/biosynthesis; Transcription Factors/physiology; Alzheimer's disease; Cyclooxygenases; Inflammation; Microglia; NSAIDs; Peroxisome proliferator-activated receptors; Neuroscience (all); Aging; Neurology (clinical); Developmental Biology; Geriatrics and Gerontology; General Neuroscience

Abstract :

[en] The role of inflammatory processes in the brains of Alzheimer's Disease (AD) patients has recently attracted considerable interest. Indeed, the only demonstrated effective therapy for AD patients is long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs). The mechanistic basis of the efficacy of NSAIDs in AD remains unclear. However, the recent recognition that NSAIDs can bind to and activate the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma), has offered an explanation for the action of these drugs in AD. PPARgamma activation leads to the inhibition of microglial activation and the expression of a broad range of proinflammatory molecules. The newly appreciated anti-inflammatory actions of PPARgamma agonists may allow novel therapies for AD and other CNS indications with an inflammatory component.

Disciplines :

Neurology

Author, co-author :

Landreth, Gary E.; Department of Neurosciences, Alzheimer Research Laboratory, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA. gel2@po.cwru.edu

HENEKA, Michael ; Department of Neurology, University of Bonn, 53105 Bonn, Germany

External co-authors :

yes

Language :

English

Title :

Anti-inflammatory actions of peroxisome proliferator-activated receptor gamma agonists in Alzheimer's disease.

Publication date :

2001

Journal title :

Neurobiology of Aging

ISSN :

0197-4580

eISSN :

1558-1497

Publisher :

Elsevier BV, United States

Volume :

Issue :

Pages :

937 - 944

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S0197-4580(01)00296-2?httpAccept=text/xml

Available on ORBilu :

since 16 May 2024

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168

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157

Bibliography

Akiyama H., Barger S., Barnum S., Bradt B., Bauer J., Cole G.M., Cooper N.R., Eikelenboom P., Emmerling M., Fiebich B.L., Finch C.E., Frautschy S., Griffin W.S., Hampel H., Hull M., Landreth G., Lue L., Mrak R., Mackenzie I.R., McGeer P.L., O'Banion M.K., Pachter J., Pasinetti G., Plata-Salaman C., Rogers J., Rydel R., Shen Y., Streit W., Strohmeyer R., Tooyoma I., Van Muiswinkel F.L., Veerhuis R., Walker D., Webster S., Wegrzyniak B., Wenk G., Wyss-Coray T. (2000) Inflammation and Alzheimer's disease. Neurobiol Aging 21:383-421.
Anthony J.C., Breitner J.C., Zandi P.P., Meyer M.R., Jurasova I., Norton M.C., Stone S.V. (2000) Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists: The Cache County study. Neurology 54:2066-2071.
Bamberger M., Landreth G. (2001) Microglial Interaction with b-Amyloid - Implications for the pathogenesis of Alzheimer's disease. Microsc Res & Tech 54:59-70.
Bernardo A., Levi G., Minghetti L. (2000) Role of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its natural ligand 15-deoxy-Delta12, 14-prostaglandin J2 in the regulation of microglial functions. Eur J Neurosci 12:2215-2223.
Blumberg B., Evans R.M. (1998) Orphan nuclear receptors - New ligands and new possibilities. Genes Dev 12:3149-3155.
Bornemann K.D., Wiederhold K.H., Pauli C., Ermini F., Stalder M., Schnell L., Sommer B., Jucker M., Staufenbiel M. (2001) Abeta-induced inflammatory processes in microglia cells of APP23 transgenic mice. Am J Pathol 158:63-73.
Breitner J.C. (1996) The role of anti-inflammatory drugs in the prevention and treatment of Alzheimer's disease. Annu Rev Med 47:401-411.
Breitner J.C., Gau B.A., Welsh K.A., Plassman B.L., McDonald W.M., Helms M.J., Anthony J.C. (1994) Inverse association of anti-inflammatory treatments and Alzheimer's disease: Initial results of a co-twin control study. Neurology 44:227-232.
Broe G.A., Grayson D.A., Creasey H.M., Waite L.M., Casey B.J., Bennett H.P., Brooks W.S., Halliday G.M. (2000) Anti-inflammatory drugs protect against Alzheimer disease at low doses. Arch Neurol 57:1586-1591.
Chattopadhyay N., Singh D.P., Heese O., Godbole M.M., Sinohara T., Black P.M., Brown E.M. (2000) Expression of peroxisome proliferator-activated receptors (PPARS) in human astrocytic cells: PPARgamma agonists as inducers of apoptosis. J Neurosci Res 61:67-74.
Chawla A., Barak Y., Nagy L., Liao D., Tontonoz P., Evans R.M. (2001) PPAR-gamma dependent, and independent effects on macrophage-gene expression in lipid metabolism, and inflammation. Nat Med 7:48-52.
Chung S.W., Kang B.Y., Kim S.H., Pak Y.K., Cho D., Trinchieri G., Kim T.S. (2000) Oxidized low density lipoprotein inhibits interleukin-12 (IL-12) production in lipopolysaccharide-activated mouse macrophages via direct interactions between peroxisome proliferator-activated receptor-gamma and nuclear factor-kappa B. J Biol Chem 275:32681-32687.
Colville-Nash P.R., Qureshi S.S., Willis D., Willoughby D.A. (1998) Inhibition of inducible nitric oxide synthase by peroxisome proliferator-activated receptor agonists: Correlation with induction of heme oxygenase 1. J Immunol 161:978-984.
Combs C., Bates P., Karlo J., Landreth G. (2001) Regulation of beta-amyloid stimulated proinflammatory responses by peroxisome proliferator-activated receptor alpha. Neurochem Intl, in press; .
Combs C.K., Johnson D.E., Karlo J.C., Cannady S.B., Landreth G.E. (2000) Inflammatory mechanisms in Alzheimer's disease: Inhibition of beta-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARgamma agonists. J Neurosci 20:558-567.
Combs C.K., Johnson D.J., Cannady S.B., Lehman T.M., Landreth G.E. (1999) Identification of microglial signal transduction pathways mediating a neurotoxic response to amyloidogenic fragments of β-amyloid and prion proteins. J Neurosci 19:928-939.
Cullingford T.E., Bhakoo K., Peuchen S., Dolphin C.T., Patel R., Clark J.B. (1998) Distribution of mRNAs encoding the peroxisome proliferator-activated receptor alpha, beta, and gamma and the retinoid X receptor alpha, beta, and gamma in rat central nervous system. J Neurochem 70:1366-1375.
Delerive P., De Bosscher K., Besnard S., Vanden Berghe W., Peters J.M., Gonzalez F.J., Fruchart J.C., Tedgui A., Haegeman G., Staels B. (1999) Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. J Biol Chem 274:32048-32054.
Delerive P., Fruchart J.C., Staels B. (2001) Peroxisome proliferator-activated receptors in inflammation control. J Endocrinol 169:453-459.
Delerive P., Gervois P., Fruchart J.C., Staels B. (2000) Induction of IkappaBalpha expression as a mechanism contributing to the anti-inflammatory activities of peroxisome proliferator-activated receptor-alpha activators. J Biol Chem 275:36703-36707.
Desvergne B., Wahli W. (1999) Peroxisome proliferator-activated receptors: Nuclear control of metabolism. Endocr Rev 20:649-688.
Fitch M.T., Doller C., Combs C.K., Landreth G.E., Silver J. (1999) Cellular and molecular mechanisms of glial scarring and progressive cavitation: In vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. J Neurosci 19:8182-8198.
Forman B.M., Tontonoz P., Chen J., Brun R.P., Spiegelman B.M., Evans R.M. (1995) 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 83:803-812.
Gelman L., Fruchart J.C., Auwerx J. (1999) An update on the mechanisms of action of the peroxisome proliferator-activated receptors (PPARs) and their roles in inflammation and cancer. Cell Mol Life Sci 55:932-943.
Gilroy D.W., Colville-Nash P.R., Willis D., Chivers J., Paul-Clark M.J., Willoughby D.A. (1999) Inducible cyclooxygenase may have anti-inflammatory properties. Nat Med 5:698-701.
Heneka M.T., Feinstein D.L. (2001) Expression and function of inducible nitric oxide synthase in neurons. J Neuroimmunol 114:8-18.
Heneka M.T., Feinstein D.L., Galea E., Gleichmann M., Wullner U., Klockgether T. (1999) Peroxisome proliferator-activated receptor gamma agonists protect cerebellar granule cells from cytokine-induced apoptotic cell death by inhibition of inducible nitric oxide synthase. J Neuroimmunol 100:156-168.
Heneka M.T., Klockgether T., Feinstein D.L. (2000) Peroxisome proliferator-activated receptor-gamma ligands reduce neuronal inducible nitric oxide synthase expression and cell death in vivo. J Neurosci 20:6862-6867.
Inoue H., Tanabe T., Umesono K. (2000) Feedback control of cyclooxygenase-2 expression through PPARgamma. J Biol Chem 275:28028-28032.
Jiang C., Ting A.T., Seed B. (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82-86.
Kalaria R.N. (1999) Microglia and Alzheimer's disease. Curr Opin Hematol 6:15-24.
Kitamura Y., Kakimura J., Matsuoka Y., Nomura Y., Gebicke-Haerter P.J., Taniguchi T. (1999) Activators of peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibit inducible nitric oxide synthase expression but increase heme oxygenase-1 expression in rat glial cells. Neurosci Lett 262:129-132.
Kitamura Y., Shimohama S., Koike H., Kakimura J., Matsuoka Y., Nomura Y., Gebicke-Haerter P.J., Taniguchi T. (1999) Increased expression of cyclooxygenases and peroxisome proliferator-activated receptor-gamma in Alzheimer's disease brains. Biochem Biophys Res Commun 254:582-586.
Kitamura Y., Taniguchi T., Kimura H., Nomura Y., Gebicke-Haerter P.J. (2000) IL-4-inhibited mRNA expression in mixed rat glial, and in isolated microglial cultures. J Neuroimmunol 106:95-104.
Lehmann J.M., Lenhard J.M., Oliver B.B., Ringold G.M., Kliewer S.A. (1997) Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem 272:3406-3410.
Li M., Pascual G., Glass C.K. (2000) Peroxisome proliferator-activated receptor gamma-dependent repression of the inducible nitric oxide synthase gene. Mol Cell Biol 20:4699-4707.
Lim G.P., Yang F., Chu T., Chen P., Beech W., Teter B., Tran T., Ubeda O., Ashe K.H., Frautschy S.A., Cole G.M. (2000) Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J Neurosci 20:5709-5714.
Lohray B.B., Bhushan V., Reddy A.S., Rao P.B., Reddy N.J., Harikishore P., Haritha N., Vikramadityan R.K., Chakrabarti R., Rajagopalan R., Katneni K. (1999) Novel euglycemic and hypolipidemic agents. 4. Pyridyl- and quinolinyl-containing thiazolidinediones. J Med Chem 42:2569-2581.
Mackenzie I.R., Munoz D.G. (1998) Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. Neurology 50:986-990.
McDonald D., Bamberger M., Combs C., Landreth G. (1998) β-amyloid fibril activate parallel mitogen-activated protein kinase pathways in microglia, and THP-1 monocytes. J Neurosci 18:4451-4460.
McDonald D.R., Brunden K.R., Landreth G.E. (1997) Amyloid fibrils activate tyrosine kinase-dependent signaling and superoxide production in microglia. J Neurosci 17:2284-2294.
McGeer P.L., Kawamata T., Walker D.G., Akiyama H., Tooyama I., McGeer E.G. (1993) Microglia in degenerative neurological disease. Glia 7:84-92.
McGeer P.L., Schulzer M., McGeer E.G. (1996) Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: A review of 17 epidemiologic studies. Neurology 47:425-432.
Moore K.J., Rosen E.D., Fitzgerald M.L., Randow F., Andersson L.P., Altshuler D., Milstone D.S., Mortensen R.M., Spiegelman B.M., Freeman M.W. (2001) The role of PPAR-gamma in macrophage differentiation and cholesterol uptake. Nat Med 7:41-47.
Murao K., Ohyama T., Imachi H., Ishida T., Cao W.M., Namihira H., Sato M., Wong N.C., Takahara J. (2000) TNF-alpha stimulation of MCP-1 expression is mediated by the Akt/PKB signal transduction pathway in vascular endothelial cells. Biochem Biophys Res Commun 276:791-796.
Murphy G.J., Holder J.C. (2000) PPAR-gamma agonists: Therapeutic role in diabetes, inflammation, and cancer. Trends Pharmacol Sci 21:469-474.
Nagy L., Tontonoz P., Alvarez J.G., Chen H., Evans R.M. (1998) Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. Cell 93:229-240.
Nolte R.T., Wisely G.B., Westin S., Cobb J.E., Lambert M.H., Kurokawa R., Rosenfeld M.G., Willson T.M., Glass C.K., Milburn M.V. (1998) Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature 395:137-143.
Ogawa O., Umegaki H., Sumi D., Hayashi T., Nakamura A., Thakur N.K., Yoshimura J., Endo H., Iguchi A. (2000) Inhibition of inducible nitric oxide synthase gene expression by indomethacin or ibuprofen in beta-amyloid protein-stimulated J774 cells. Eur J Pharmacol 408:137-141.
Olefsky J.M. (2000) Treatment of insulin resistance with peroxisome proliferator-activated receptor gamma agonists. J Clin Invest 106:467-472.
Pasinetti G.M., Aisen P.S. (1998) Cyclooxygenase-2 expression is increased in frontal cortex of Alzheimer's disease brain. Neuroscience 87:319-324.
Perlmutter L.S., Barron E., Chui H.C. (1990) Morphologic association between microglia and senile plaque amyloid in Alzheimer's disease. Neurosci Lett 119:32-36.
Petrova T.V., Akama K.T., Van Eldik L.J. (1999) Cyclopentenone prostaglandins suppress activation of microglia: Down- regulation of inducible nitric-oxide synthase by 15-deoxy-Delta12,14- prostaglandin J2. Proc Natl Acad Sci USA 96:668-673.
Reddy K.A., Lohray B.B., Bhushan V., Reddy A.S., Rao Mamidi N.V., Reddy P.P., Saibaba V., Reddy N.J., Suryaprakash A., Misra P., Vikramadithyan R.K., Rajagopalan R. (1999) Novel antidiabetic and hypolipidemic agents. 5. Hydroxyl versus benzyloxy containing chroman derivatives. J Med Chem 42:3265-3278.
Rich J.B., Rasmusson D.X., Folstein M.F., Carson K.A., Kawas C., Brandt J. (1995) Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology 45:51-55.
Ricote M., Huang J., Fajas L., Li A., Welch J., Najib J., Witztum J.L., Auwerx J., Palinski W., Glass C.K. (1998) Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc Natl Acad Sci USA 95:7614-7619.
Ricote M., Huang J.T., Welch J.S., Glass C.K. (1999) The peroxisome proliferator-activated receptor (PPARgamma) as a regulator of monocyte/macrophage function. J Leukoc Biol 66:733-739.
Ricote M., Li A.C., Willson T.M., Kelly C.J., Glass C.K. (1998) The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391:79-82.
Rogers J., Webster S., Lue L.F., Brachova L., Civin W.H., Emmerling M., Shivers B., Walker D., McGeer P. (1996) Inflammation and Alzheimer's disease pathogenesis. Neurobiol Aging 17:681-686.
Rossi A., Kapahi P., Natoli G., Takahashi T., Chen Y., Karin M., Santoro M.G. (2000) Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase. Nature 403:103-108.
Sainati S., Ingram D., Talwalker G., Geis G. (2000) Results of a double-blind, randomized, placebo-controlled study of celecoxib in the treatment of Alzheimer's Disease. Sixth International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy 180.
Steppan C.M., Bailey S.T., Bhat S., Brown E.J., Banerjee R.R., Wright C.M., Patel H.R., Ahima R.S., Lazar M.A. (2001) The hormone resistin links obesity to diabetes. Nature 409:307-312.
Stewart W.F., Kawas C., Corrada M., Metter E.J. (1997) Risk of Alzheimer's disease and duration of NSAID use. Neurology 48:626-632.
Straus D.S., Pascual G., Li M., Welch J.S., Ricote M., Hsiang C.H., Sengchanthalangsy L.L., Ghosh G., Glass C.K. (2000) 15-Deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappa B signaling pathway. Proc Natl Acad Sci USA 97:4844-4849.
Subbaramaiah K., Lin D.T., Hart J.C., Dannenberg A.J. (2001) Peroxisome proliferator-activated receptor gamma ligands suppress the transcriptional activation of cyclooxygenase-2: Evidence for involvement of activator protein-1 and CREB-binding protein/p300. J Biol Chem 276:12440-12448.
Tontonoz P., Nagy L., Alvarez J.G., Thomazy V.A., Evans R.M. (1998) PPARgamma promotes monocyte/macrophage differentiation, and uptake of oxidized LDL. Cell 93:241-252.
Uppenberg J., Svensson C., Jaki M., Bertilsson G., Jendeberg L., Berkenstam A. (1998) Crystal structure of the ligand binding domain of the human nuclear receptor PPARgamma. J Biol Chem 273:31108-31112.
Vodovotz Y., Lucia M.S., Flanders K.C., Chesler L., Xie Q.W., Smith T.W., Weidner J., Mumford R., Webber R., Nathan C., Roberts A.B., Lippa C.F., Sporn M.B. (1996) Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease. J Exp Med 184:1425-1433.
Willson T.M., Brown P.J., Sternbach D.D., Henke B.R. (2000) The PPARs: From orphan receptors to drug discovery. J Med Chem 43:527-550.
Willson T.M., Wahli W. (1997) Peroxisome proliferator-activated receptor agonists. Curr Opin Chem Biol 1:235-241.
Yin M.J., Yamamoto Y., Gaynor R.B. (1998) The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature 396:77-80.
Yu K., Bayona W., Kallen C.B., Harding H.P., Ravera C.P., McMahon G., Brown M., Lazar M.A. (1995) Differential activation of peroxisome proliferator-activated receptors by eicosanoids. J Biol Chem 270:23975-23983.