A5010541195- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Neurological diseases and metabolism
- Prion Diseases and Protein Misfolding
- Botulinum Toxin and Related Neurological Disorders
- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
- CRISPR and Genetic Engineering
- Click Chemistry and Applications
- Stress Responses and Cortisol
- Endoplasmic Reticulum Stress and Disease
- Tryptophan and brain disorders
- Neuroscience and Neuropharmacology Research
- Telomeres, Telomerase, and Senescence
- Nuclear Receptors and Signaling
- Nerve injury and regeneration
- Mitochondrial Function and Pathology
- Circadian rhythm and melatonin
- Toxoplasma gondii Research Studies
- Calcium signaling and nucleotide metabolism
- Bipolar Disorder and Treatment
- Viral Infections and Immunology Research
- Neonatal Health and Biochemistry
- Genetics, Aging, and Longevity in Model Organisms
University of Toronto
2019-2025
Occupational Cancer Research Centre
2019-2025
Discovery Centre
2023
Canada Research Chairs
2019
Hong Kong University of Science and Technology
2015-2019
University of Hong Kong
2015-2019
Columbia University
2018
Abstract Background Multiple system atrophy (MSA) is a neurodegenerative condition characterized by variable combinations of parkinsonism, autonomic failure, cerebellar ataxia and pyramidal features. Although the distribution synucleinopathy correlates with predominant clinical features, burden pathology does not fully explain observed differences in presentation rate disease progression. We hypothesized that heterogeneity MSA consequence variability seeding activity α-synuclein both between...
Abstract Selective autophagy is an essential process to maintain cellular homeostasis through the constant recycling of damaged or superfluous components. Over a dozen selective pathways mediate degradation diverse substrates, but whether these can influence one another remains unknown. We address this question using pexophagy, autophagic peroxisomes, as model. show in cells that upregulated pexophagy impairs both mitochondria and protein aggregates by exhausting initiation factor, ULK1....
Highlights•α-syn binds to and anchors G6PD synaptic vesicles•α-syn fibrilization inhibits function impairs redox homeostasis•Loss of phenocopies Parkinson's disease•Restoration activity rescues dopamine signaling in diseaseSummaryLoss dopaminergic neurons disease (PD) is preceded by loss (DA) accumulation proteinaceous aggregates. Linking these deficits critical restoring DA PD. Using murine human pluripotent stem cell (hPSC) models PD coupled with postmortem tissue, we show that α-syn...
Abstract Unique strains of α-synuclein aggregates have been postulated to underlie the spectrum clinical and pathological presentations seen across synucleinopathies. Whereas multiple system atrophy (MSA) is associated with a predominance oligodendroglial inclusions, in Parkinson’s disease (PD) preferentially accumulate neurons. The G51D mutation SNCA gene encoding causes an aggressive, early-onset form PD that exhibits neuropathological traits reminiscent both MSA. To assess strain...
Activating transcription factor 4 (ATF4) plays important physiologic roles in the brain including regulation of learning and memory as well neuronal survival death. Yet, outside translational by eIF2α-dependent stress response pathway, there is little information about how its levels are controlled neurons. Here, we show that brain-derived neurotrophic (BDNF) promotes a rapid sustained increase ATF4 transcripts protein levels. This dependent on tropomyosin receptor kinase (TrkB) signaling,...
Depression is a prevalent mental illness in developed countries. In Western medicine, experimental and clinical investigations have demonstrated that depression associated with the dysregulation of neurotransmitter signaling, symptoms can be alleviated by therapeutic intervention. However, patients taking antidepressant drugs often experience serious side effects high relapse rates. On other hand, traditional Chinese medicine (TCM) views as manifestation liver qi stagnation. Practitioners...
The cellular prion protein, PrP C , has been postulated to function as a receptor for α-synuclein, potentially facilitating cell-to-cell spreading and/or toxicity of α-synuclein aggregates in neurodegenerative disorders such Parkinson's disease. To test this hypothesis, we compared the propagation behavior two different aggregate strains M83 transgenic mice that either expressed or did not express . Following intracerebral inoculation with S NS strain, presence had minimal influence on...
The cellular prion protein, PrP C , has been postulated to function as a receptor for α-synuclein, potentially facilitating cell-to-cell spreading and/or toxicity of α-synuclein aggregates in neurodegenerative disorders such Parkinson’s disease. Previously, we generated the “Salt (S)” and “No Salt (NS)” strains that cause distinct pathological phenotypes M83 transgenic mice overexpressing A53T-mutant human α-synuclein. To test hypothesis facilitates propagation aggregates, produced either...
Abstract Several in vitro and vivo findings have consistently shown that α-synuclein derived from multiple system atrophy (MSA) subjects has more seeding capacity than Parkinson’s disease-derived α-synuclein. However, reliable detection of MSA using seeded amplification assays, such as the Real-Time Quaking-induced Conversion, remained challenging. Here we demonstrate interaction Thioflavin T dye with disease patients can be modulated by type salt, pH, ionic strength used to generate...
Abstract Selective autophagy is an essential mechanism to maintain organelle integrity and cellular homeostasis through the constant recycling of damaged or superfluous components. While distinct selective pathways mediate degradation diverse substrates including organelles pathogens, whether these can influence one another remains unknown. We address this question here using pexophagy, autophagic peroxisomes, as a model. demonstrate in cells that upregulated pexophagy exhausts limits both...
The risk of developing Alzheimer's disease (AD) is almost double in patients with insulin resistance. Prolong hyperinsulinemia a major cause We presented last year that peripheral and resistance alters the biology function neurons at early stages. Mechanistically, we showed failure prompt glucose metabolism due to loss hexokinase-2 (HK2) impairs multi-step pathway results reactivation cell cycle machinery, as well accumulation signals phosphorylated tau amyloid. Despite all these cellular...