A5017451863- Parkinson's Disease Mechanisms and Treatments
- Cancer Genomics and Diagnostics
- Microtubule and mitosis dynamics
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Advanced biosensing and bioanalysis techniques
- Neurological disorders and treatments
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Cholinesterase and Neurodegenerative Diseases
- Neurological diseases and metabolism
- Dendrimers and Hyperbranched Polymers
- Cellular transport and secretion
- Nuclear Receptors and Signaling
- Microbial Metabolic Engineering and Bioproduction
- Biotin and Related Studies
- Synthesis and Characterization of Heterocyclic Compounds
- Genetics, Bioinformatics, and Biomedical Research
- Nerve injury and regeneration
- Lipoproteins and Cardiovascular Health
- biodegradable polymer synthesis and properties
- RNA Interference and Gene Delivery
University of Michigan
2021-2024
Brigham and Women's Hospital
2021-2023
Harvard University
2021-2023
Abstract In Parkinson’s disease and other synucleinopathies, the elevation of α-synuclein phosphorylated at Serine129 (pS129) is a widely cited marker pathology. However, physiological role for pS129 has remained undefined. Here we use multiple approaches to show first time that functions as regulator neuronal activity. Neuronal activity triggers sustained increase in cultured neurons (200% within 4 h). accord, brain elevated environmentally enriched mice exhibiting enhanced long-term...
Increasing evidence has shown that Parkinson's disease (PD) impairs midbrain dopaminergic, cortical and other neuronal subtypes in large part due to the build-up of lipid- vesicle-rich α-synuclein (αSyn) cytotoxic inclusions. We previously identified stearoyl-CoA desaturase (SCD) as a potential therapeutic target for synucleinopathies. A brain-penetrant SCD inhibitor, YTX-7739, was developed entered Phase 1 clinical trials. Here, we report efficacy YTX-7739 reversing pathological αSyn...
Protein misfolding results in a plethora of known diseases such as Alzheimer’s disease, Parkinson’s Huntington’s transthyretin-related amyloidosis, type 2 diabetes, Lewy body dementia, and spongiform encephalopathy. To provide diverse portfolio therapeutic small molecules with the ability to reduce protein misfolding, we evaluated set 13 compounds: 4-(benzo[d]thiazol-2-yl)aniline (BTA) its derivatives containing urea (1), thiourea (2), sulfonamide (3), triazole (4), triazine (5) linker. In...
Alzheimer's disease (AD) is a multifactorial, chronic neurodegenerative characterized by the presence of extracellular β-amyloid (Aβ) plaques, intraneuronal neurofibrillary tangles (NFTs), activated microglial cells, and an inflammatory state (involving reactive oxygen species production) in brain. NFTs are comprised misfolded hyperphosphorylated forms microtubule-binding protein tau. Interestingly, trimeric form 2N4R splice isoform tau has been found to be more toxic than 1N4R neuron...
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder underlying dementia in geriatric population. AD manifests by two pathological hallmarks: extracellular amyloid-β (Aβ) peptide-containing senile plaques and intraneuronal neurofibrillary tangles comprised of aggregated hyperphosphorylated tau protein (p-tau). However, more than half cases also display presence α-synuclein (α-syn)-containing Lewy bodies. Conversely, bodies disorders have been reported to concomitant Aβ...
Abstract The centromere, defined by the enrichment of CENP-A (a Histone H3 variant) containing nucleosomes, is a specialised chromosomal locus that acts as microtubule attachment site. To preserve centromere identity, levels must be maintained through active loading during cell cycle. A central player mediating this process Mis18 complex (Mis18α, Mis18ý and Mis18BP1), which recruits specific chaperone HJURP to centromeres for deposition. Here, using multi-pronged approach, we characterise...
The neuronal protein α‐synuclein is centrally involved in the neurodegeneration occurring Parkinson's disease and related synucleinopathies. α‐Synuclein's membrane‐induced 3–11 helix conformation has a hydrophobic membrane‐embedded half hydrophilic cytosolic half. Here, we studied significance of (a) surprising hydrophobicity amino‐acids at cytosol‐exposed position 8; (b) absence positively charged lysine/arginine from all positions (1‐5‐8‐9). We found that further increasing or adding...