A5103105581- Alzheimer's disease research and treatments
- Amyotrophic Lateral Sclerosis Research
- Cholinesterase and Neurodegenerative Diseases
- Sirtuins and Resveratrol in Medicine
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Neuroinflammation and Neurodegeneration Mechanisms
- Biochemical effects in animals
- Ginkgo biloba and Cashew Applications
- Parkinson's Disease Mechanisms and Treatments
- Ubiquitin and proteasome pathways
- Neuroscience and Neuropharmacology Research
- Biotin and Related Studies
- Endoplasmic Reticulum Stress and Disease
- Neurogenetic and Muscular Disorders Research
Gladstone Institutes
2011-2022
Stone Clinic
2018
University of California, San Francisco
2014-2017
Tau (MAPT) drives neuronal dysfunction in Alzheimer disease (AD) and other tauopathies. To dissect the underlying mechanisms, we combined an engineered ascorbic acid peroxidase (APEX) approach with quantitative affinity purification mass spectrometry (AP-MS) followed by proximity ligation assay (PLA) to characterize interactomes modified activity mutations that cause frontotemporal dementia (FTD) human induced pluripotent stem cell (iPSC)-derived neurons. We established interactions of...
The ubiquitin-proteasome system (UPS) is responsible for most selective protein degradation in eukaryotes and regulates numerous cellular processes, including cell cycle control quality control. A component of this system, the deubiquitinating enzyme USP14, associates with proteasome where it can rescue substrates from by removal ubiquitin tag. We previously found that a small-molecule inhibitor known as IU1, increase rate subset substrates. report here synthesis characterization 87 variants...
Hyperacetylation of tau has been implicated in neurodegeneration and cognitive decline tauopathy brains. The nicotinamide adenosine dinucleotide-dependent class-III protein deacetylase SIRT1 is one the major enzymes involved removal acetyl groups from vitro . However, whether regulates acetylation pathogenic ameliorates tau-mediated pathogenesis remains unclear. Here, we report deacetylating activity for acetylated Lys174 (K174) tauP301S transgenic mice with a brain-specific deletion. We...
Abstract Introduction Frontotemporal lobar degeneration–causing mutations in the progranulin ( GRN ) gene reduce protein (PGRN) levels, suggesting that restoring PGRN mutation carriers may be therapeutic. Nimodipine, a Food and Drug Administration–approved blood‐brain barrier‐penetrant calcium channel blocker, increased levels PGRN‐deficient murine models. We sought to assess safety tolerability of oral nimodipine human carriers. Methods performed an open‐label, 8‐week, dose‐finding, phase 1...
SUMMARY Tau (MAPT) drives neuronal dysfunction in Alzheimer’s disease (AD) and other tauopathies. To dissect the underlying mechanisms, we combined an engineered ascorbic acid peroxidase (APEX) approach with quantitative affinity purification mass spectrometry (AP-MS) followed by proximity ligation assay (PLA) to characterize interactomes modified activity mutations that cause frontotemporal dementia (FTD) human induced pluripotent stem cell (iPSC)-derived neurons. We established...
Tauopathies are a group of neurodegenerative diseases, including frontotemporal dementia (FTD) and Alzheimer's disease (AD) that characterized by accumulation hyperphosphorylated tau fibrils. Emerging evidence suggests intermediate oligomers, not fibrils, key players in tau-mediated neurodegeneration. However, the mechanisms underlying oligomeric neurodegeneration remain largely unknown. Lysine acetylation modulates diverse biological processes, protein stability protein-protein interaction....
The microtubule binding protein tau promotes the assembly and stabilization of microtubules. Accumulation aberrantly phosphorylated (p-tau) may underlie tau-mediated neurodegeneration by disrupting ability to bind microtubules promoting aggregation fibrillization in neurodegenerative tauopathies. Suppressing endogenous soluble or transgenic improves cognitive function mouse models Alzheimer's disease (AD) frontotemporal dementia parkinsonism linked chromosome 17 (FTDP-17), respectively....