A5078304084- Genetics, Aging, and Longevity in Model Organisms
- Endoplasmic Reticulum Stress and Disease
- Prion Diseases and Protein Misfolding
- Cytomegalovirus and herpesvirus research
- Cancer Cells and Metastasis
- Protein Degradation and Inhibitors
- 3D Printing in Biomedical Research
- Parkinson's Disease Mechanisms and Treatments
- Circadian rhythm and melatonin
- Pesticide Exposure and Toxicity
- Diabetes and associated disorders
- Biochemical Acid Research Studies
- Phagocytosis and Immune Regulation
- Spaceflight effects on biology
- Alzheimer's disease research and treatments
- Heat shock proteins research
- Calcium signaling and nucleotide metabolism
- Cell Adhesion Molecules Research
- Ubiquitin and proteasome pathways
- Blood properties and coagulation
- CRISPR and Genetic Engineering
- Cellular transport and secretion
- Pluripotent Stem Cells Research
- Escherichia coli research studies
- Biomedical Research and Pathophysiology
Harvard University
2023-2024
Precision Therapeutics (United States)
2024
Massachusetts General Hospital
2023-2024
Hospital Municipal Souza Aguiar
2024
DKFZ-ZMBH Alliance
2019-2022
Heidelberg University
2019-2022
German Cancer Research Center
2019-2022
Article25 May 2020Open Access Source DataTransparent process The HSP110/HSP70 disaggregation system generates spreading-competent toxic α-synuclein species Jessica Tittelmeier Center for Molecular Biology of Heidelberg University (ZMBH) and German Cancer Research (DKFZ), DKFZ-ZMBH Alliance, Heidelberg, Germany Search more papers by this author Carl Alexander Sandhof Heidrun Maja Ries Silke Druffel-Augustin Axel Mogk Bernd Bukau Carmen Nussbaum-Krammer Corresponding Author [email protected]...
Aging is associated with a gradual decline of cellular proteostasis, giving rise to devastating protein misfolding diseases, such as Alzheimer disease (AD) or Parkinson (PD). These diseases often exhibit complex pathology involving non-cell autonomous proteotoxic effects, which are still poorly understood. Using Caenorhabditis elegans we investigated how local affecting neighboring cells and tissues showing that misfolded PD-associated SNCA/α-synuclein accumulating in highly dynamic...
Cerebral cortical-enriched organoids derived from human pluripotent stem cells (hPSCs) are valuable models for studying neurodevelopment, disease mechanisms, and therapeutic development. However, recognized limitations include the high variability of across hPSC donor lines experimental replicates. We report a 96-slitwell method efficient, scalable, reproducible cortical organoid production. When hPSCs were cultured with controlled-release FGF2 an SB431542 concentration appropriate their
The chaperone-mediated sequestration of misfolded proteins into inclusions is a pivotal cellular strategy to maintain proteostasis in Saccharomyces cerevisiae, executed by small heat shock (sHsps) Hsp42 and Btn2. Direct homologs Btn2 are absent other organisms, questioning whether represents conserved and, if so, which factors involved. We examined sHsps from Escherchia coli, Caenorhabditis elegans, humans for their ability complement the defects yeast sequestrase mutants. show that an...
Abstract Numerous studies have implicated endolysosomal dysfunction in Alzheimer’s disease (AD) and related tauopathies. However, the mechanisms driving these disturbances remain poorly understood. Using C. elegans , we recently identified genes involved sphingolipid metabolism as crucial for maintenance of integrity. Abnormal is increasingly reported AD, but its impact on Tau pathology remains unclear. Here, investigated role membrane homeostasis effect aggregation toxicity human cell...
Abstract The spreading of Tau pathology is closely associated with the progression neurodegeneration and cognitive decline in Alzheimer’s disease other tauopathies. A key event this process rupture endolysosomal vesicles following intercellular transfer aggregates, releasing transferred species into cytosol where they can promote aggregation endogenous Tau. However, understanding cellular pathways involved remains limited. In study, we investigated that prevent vesicle rupture. We...
Abstract Background Human pluripotent stem cell (hPSC)‐derived brain organoids patterned towards the cerebral cortex are valuable models of interactions occurring in vivo cortical tissue. We and others have used these to model dominantly inherited FTD‐tau. While studies provided essential insights, organoid yet reach their full potential. Studies hindered by well‐recognized hurdles: low production efficiency high variability between individual organoids, across lines, experiments. A protocol...
ABSTRACT The gradual accumulation and prion-like propagation of α-synuclein other amyloidogenic proteins is associated with devastating neurodegenerative diseases. metazoan disaggregation machinery, a specific combination HSP70 its co-chaperones, able to disassemble fibrils in vitro , but the physiological consequence vivo unknown. To explore this, we used Caenorhabditis elegans models that exhibit pathological features α-synuclein, such as misfolding, intercellular spreading toxicity. We...