Pathophysiological study of synaptic vesicle protein synaptogyrin3 (SYNGR3) in Parkinson's disease. Health and Medical Research Fund (HMRF), Food & Health Bureau, HKSAR Government (Jan 2018) Therapeutic effects of brain-penetrable inhibitors to prevent accumulation of pathogenic alpha-synuclein Therapeutic effects of Saracatinib to prevent accumulation of alpha synuclein in Parkinson’s disease. Health and Medical Research Fund (HMRF), Food & Health Bureau, HKSAR Government (August 2013) Pathophysiological study of Parkinson's disease associated with leucine-rich repeat kinase 2 (LRRK2) gene mutation Annals of Clinical and Translational Neurology. (2014) LRRK2 R1441G mice are more liable to dopamine depletion and locomotor inactivity. Liu HF, Lu S, Ho PWL, Tse HM, Pang SYY, Kung MHW, Ho JWM, Ramsden DB, Zhou ZJ, Ho SL.(2016) Phos-tag analysis of Rab10 phosphorylation by LRRK2: a powerful assay for assessing kinase function and inhibitors. Ito G, Katsemonova K, Tonelli F, Lis P, Baptista M, Shpiro N, Duddy G, Wilson S, Ho PW, Ho SL, Reith AD, Alessi D.(2017) Combined LRRK2 mutation, aging and chronic low dose oral rotenone as a model of Parkinson's disease. Liu HF, Ho PW, Leung GC, Lam CS, Pang SY, Li L, Kung MH, Ramsden DB, Ho SL.(2017) Burden of rare variants in ALS genes influences survival in familial and sporadic ALS. Pang SY, Hsu JS, Teo KC, Li Y, Kung MHW, Cheah KSE, Chan D, Cheung KMC, Li MX, Sham PC, Ho SL.(2017) The role of gene variants in the pathogenesis of neurodegenerative disorders as revealed by next generation sequencing studies: a review. Pang SY, Teo KC, Hsu JS, Chang RSK, Li MX, Sham PC, Ho SL.(2018) Development of phospho-specific Rab protein antibodies to monitor in vivo activity of the LRRK2 Parkinson's disease kinase. Lis P, Burel S, Steger M, Mann M, Brown F, Diez F, Tonelli F, Holton JL, Ho PW, Ho SL, Chou MY, Polinski NK, Martinez TN, Davies P, Alessi DR.(2019) Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson's disease: role for therapeutic activation of chaperone-mediated autophagy (CMA). Ho PWL, Leung MCT, Liu HF, Pang SYY, Lam CSC, Xian JW, Li LF, Kung MHW, Ramsden DB, Ho SL.The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson’s disease. Pang SYY, Ho PWL, Liu HF, Leung CT, Li LF, Chang EES, Ramsden DB, Ho SL.Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2 R1441G mice. Liu HF, Ho PWL, Leung CT, Pang SY, Chang EES, Choi ZY, Kung MH, Ramsden DB, Ho SL.Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Klionsky DJ, Abdel-Aziz AK, Abdelfatah S,…Leung GCT,…Liu HF…,Ho, PWL, Ho SL,… Ramsden DB…Sluimer JC, Stallings CL, Tong CK.We also elucidated how UCP4 interacted with mitochondrial Complex II to preserve ATP synthesis under cellular stress. In parallel studies, we described the beneficial effects of leptin (a regulator of metabolism) on neuronal survival being mediated via UCP2, supporting a link between metabolic pathways and pathogenic processes in PD. Our studies uncovered a novel link between UCPs and nuclear-factor kappa-B (NF- k B), and more specifically the c-Rel pro-survival pathway, which can be a potential therapeutic target in PD. We have developed methods and materials including antibodies to human neuronal uncoupling proteins (UCP4 and 5).
We described and elucidated some of the neuroprotective mechanisms of mitochondrial neuronal uncoupling proteins (UCPs) in experimental models of PD. We have previously explored mitochondrial dysfunction, an important pathogenic process involved in PD. This enzyme assay can quantify the estrogenic effects of environmental pollutants, such as PCBs and plasticizers linked to cancer and neurodegeneration. This project delivered tangible materials including human COMT antibodies and a patented COMT ELISA assay containing a unique synthetic 18 amino acid polypeptide protein tag. Our earlier research described how a ubiquitous xenobiotic enzyme, catechol-O-methyltransferase (COMT) provided the link between the effects of estrogen and PD. I lead a research team in HKU focusing mainly on Parkinson's disease (PD), its etiology, pathogenesis and exploring therapeutic methods to modify these processes.
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