References of "Walter, Jonas 50003295"
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See detailAutomated high-throughput high-content autophagy and mitophagy analysis platform
Arias, Jonathan UL; Jarazo, Javier UL; Walter, Jonas UL et al

in Scientific Reports (2019)

Autophagic processes play a central role in cellular homeostasis. In pathological conditions, the flow of autophagy can be affected at multiple and distinct steps of the pathway. Current analyses tools do ... [more ▼]

Autophagic processes play a central role in cellular homeostasis. In pathological conditions, the flow of autophagy can be affected at multiple and distinct steps of the pathway. Current analyses tools do not deliver the required detail for dissecting pathway intermediates. The development of new tools to analyze autophagic processes qualitatively and quantitatively in a more straightforward manner is required. Defining all autophagy pathway intermediates in a high-throughput manner is technologically challenging and has not been addressed yet. Here, we overcome those requirements and limitations by the developed of stable autophagy and mitophagy reporter-iPSC and the establishment of a novel high-throughput phenotyping platform utilizing automated high-content image analysis to assess autophagy and mitophagy pathway intermediates. [less ▲]

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See detail3D Cultures of Parkinson's Disease‐Specific Dopaminergic Neurons for High Content Phenotyping and Drug Testing
Bolognin, Silvia UL; Fossépré, Marie; Qing, Xiaobing et al

in Advanced Science (2018)

Parkinson's disease (PD)‐specific neurons, grown in standard 2D cultures, typically only display weak endophenotypes. The cultivation of PD patient‐specific neurons, derived from induced pluripotent stem ... [more ▼]

Parkinson's disease (PD)‐specific neurons, grown in standard 2D cultures, typically only display weak endophenotypes. The cultivation of PD patient‐specific neurons, derived from induced pluripotent stem cells carrying the LRRK2‐G2019S mutation, is optimized in 3D microfluidics. The automated image analysis algorithms are implemented to enable pharmacophenomics in disease‐relevant conditions. In contrast to 2D cultures, this 3D approach reveals robust endophenotypes. High‐content imaging data show decreased dopaminergic differentiation and branching complexity, altered mitochondrial morphology, and increased cell death in LRRK2‐G2019S neurons compared to isogenic lines without using stressor agents. Treatment with the LRRK2 inhibitor 2 (Inh2) rescues LRRK2‐G2019S‐dependent dopaminergic phenotypes. Strikingly, a holistic analysis of all studied features shows that the genetic background of the PD patients, and not the LRRK2‐G2019S mutation, constitutes the strongest contribution to the phenotypes. These data support the use of advanced in vitro models for future patient stratification and personalized drug development. [less ▲]

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See detailANALYSIS OF NEURONAL DIFFERENTIATION IN GENETIC FORMS OF PARKINSON’S DISEASE REVEALS A NEURODEVELOPMENTAL CONTRIBUTION
Walter, Jonas UL

Doctoral thesis (2017)

During the mammalian embryonic neurodevelopment, all neurons descend from neuroepithelial stem cells. Accumulating evidences indicate a contribution of neurodevelopmental processes to the vulnerability to ... [more ▼]

During the mammalian embryonic neurodevelopment, all neurons descend from neuroepithelial stem cells. Accumulating evidences indicate a contribution of neurodevelopmental processes to the vulnerability to diseases. Here, we elucidate such developmental contribution in the context of Parkinson’s disease by combining high content imaging approaches, single-cell RNA sequencing, 3D image analysis, and multifactorial functional mitochondrial readouts. We found that the prominent PD-associated LRRK2-G2019S mutation accelerates dopaminergic neuron differentiation, accompanied by a reduced viability, resulting in indistinguishable dopaminergic neuron quantities. Our data indicate that the unexpected dynamics is driven by LRRK2-G2019S-dependent aberrations in gene expression as well as mitochondrial health and biogenesis of the neuroepithelial stem cell population. We conclude that LRRK2-G2019S modifies the dynamics of dopaminergic neuron fate specification during development, what may constitute a predisposition to parts of the PD-associated clinical manifestations. [less ▲]

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See detailDistinct antimicrobial peptide expression determines host species-specific bacterial associations
Franzenburg, Sören; Walter, Jonas UL; Künzel, Sven et al

in Proceedings of the National Academy of Sciences of the United States of America (2013), 110(39), 37303738

Animals are colonized by coevolved bacterial communities, which contribute to the host’s health. This commensal microbiota is often highly specific to its host-species, inferring strong selective ... [more ▼]

Animals are colonized by coevolved bacterial communities, which contribute to the host’s health. This commensal microbiota is often highly specific to its host-species, inferring strong selective pressures on the associated microbes. Several factors, including diet, mucus composition, and the immune system have been proposed as putative determinants of host-associated bacterial communities. Here we report that species-specific antimicrobial peptides account for different bacterial communities associated with closely related species of the cnidarian Hydra. Gene family extensions for potent antimicrobial peptides, the arminins, were detected in four Hydra species, with each species possessing a unique composition and expression profile of arminins. For functional analysis, we inoculated arminin-deficient and control polyps with bacterial consortia characteristic for different Hydra species and compared their selective preferences by 454 pyrosequencing of the bacterial microbiota. In contrast to control polyps, arminin-deficient polyps displayed decreased potential to select for bacterial communities resembling their native microbiota. This finding indicates that species-specific antimicrobial peptides shape species-specific bacterial associations. [less ▲]

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See detailSodium butyrate improves memory function in an Alzheimer's disease mouse model when administered at an advanced stage of disease progression
Govindarajan, Nambirajan; Agis-Balboa, Roberto Carlos; Walter, Jonas UL et al

in Journal of Alzheimer's Disease [=JAD] (2011), 26(1), 187-197

Dysregulation of histone acetylation has been implicated in the onset of age-associated memory impairment and the pathogenesis of neurodegenerative diseases. Elevation of histone acetylation via ... [more ▼]

Dysregulation of histone acetylation has been implicated in the onset of age-associated memory impairment and the pathogenesis of neurodegenerative diseases. Elevation of histone acetylation via administration of histone deacetylase (HDAC) inhibitors is currently being pursued as a novel therapeutic avenue to treat memory impairment linked to Alzheimer's disease (AD). Here we show that severe amyloid pathology correlates with a pronounced dysregulation of histone acetylation in the forebrain of APPPS1-21 mice. Importantly, prolonged treatment with the pan-HDAC inhibitor sodium butyrate improved associative memory in APPPS1-21 mice even when administered at a very advanced stage of pathology. The recovery of memory function correlated with elevated hippocampal histone acetylation and increased expression of genes implicated in associative learning. These data advance our understanding of the potential applicability of HDAC inhibitors for the treatment of AD and suggest that HDAC inhibitors may have beneficial effects even when administered long after the onset of disease-associated symptoms. [less ▲]

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