Translational Neuroscience researches on neuron degeneration in Parkinson's disease (PD), Alzheimer’s disease (AD) and other human neurodegenerative disorders.
My laboratory’s interests lie in translational studies on identification and verification of novel key molecular and therapeutic targets, signalling pathways or new effective neuro-protective agents relevant to pathogenesis and therapy of debilitating human neurodegenerative diseases, including Parkinson disease (PD), Alzheimer’s disease (AD) and other human neuron degenerative disorders.
To achieve it, cutting-edged high throughput screening works are being performed in the lab. These screening works include in vitro high throughput proteomics screening plus immuno-precipitation protocols as well as cellular & molecular biological measurements plus biochemical techniques to search for and identify new key molecular targets or novel signalling pathways relevant to pathogenesis and therapy of human neurodegenerative diseases. Furthermore in vitro high throughput chemical library screening is performed to identify novel neuro-protective agents for potential future clinical drugs developments. Findings from in vitro identification of new targets or new neuron protective agents will be strengthened and deciphered in details of their underlying molecular mechanisms as well as further validated by our established in vivo environmental or genetic Drosophila and mice human disease models. Third, direct in vivo screening using our established rapid in vivo Drosophila PD models is used to search for new genes or potential anti-PD drugs for future therapies against neuron degeneration in PD and other human neurodegenerative diseases.
Our works will not only advance our understanding of the pathogenesis of PD and other human degenerative disorders, but also can benefit patients via contributions of new therapeutic agents or strategies against neuron degeneration in PD and other human neurodegenerative diseases.
1) Zhi Dong Zhou* & Eng King Tan, Potential pathophysiological crosstalk between Parkin and FBXO7 signalling pathways. Electronical Journal of Biology. 2016. Vol. 12(4): 439-442. *, Co-Corresponding author
2) Zhi Dong Zhou*, Wuan Ting Saw, Eng King Tan. Mitochondrial CHCHD containing proteins: physiologic functions and link with neurodegenerative diseases. Molecular Neurology, in press, doi:10.1007/s12035-016-0099-5. *, Co-Corresponding author
3) Yin Xia Chao, Zhi Dong Zhou, Eng-King Tan. Comment and response: Plasma Coenzyme Q10 Levels and Multiple System Atrophy. JAMA Neurology, in press
4) Z. D. Zhou*, et al. Linking F-box protein 7 and Parkin to neuronal degeneration in Parkinson's disease (PD). Mol Brain, 2016; 9: 41. *, Co-Corresponding author
5) Angeles, D C,, Zhou ZD, et al. Antioxidants inhibit Neuronal Toxicity in Parkinson’s Disease-linked LRRK2. Annals of Clinical and Translational Neurology, 2016; 3(4): 288–294
6) Z. D. Zhou, et al. F-box protein 7 mutations promote protein aggregation in mitochondria and inhibit mitophagy. Hum Mol Genet. 2015 Nov 15;24(22):6314-30
7) Chao YX, , Zhou ZD, ,et al. Association Analysis of COQ2 Variant in Dementia and Essential Tremor. Parkinson's Disorders. Volume 2015, Article ID 926280, http://dx.doi.org/10.1155/2015/926280
8) Angeles, D C,, Zhou ZD, et al. Thiol-peroxidases ameliorate LRRK2 mutant-induced mitochondrial and dopaminergic neuronal degeneration in Drosophila. Human Molecular Genetics (2014) June 15; 23:3157-65.
9) Z.D. Zhou, et al. Mutant PINK1 up-regulates tyrosine hydroxylase and dopamine levels leading to vulnerability of dopaminergic neurons. Free Radical Biology & Medicine, 2014. 68:220-33,
10) Z.D. Zhou, et al. “Ring finger protein 146 / iduna is a Poly(ADP-ribose) polymer binding and PARsylation dependent E3 ubiquitin ligase”. Cell Adhension & Migration. 2011. 5(6):463-71
11) Z.D. Zhou, et al, LINGO-1 and neurodegeneration: pathophysiologic clues for essential tremor? Tremor and Other Hyperkinetic Movements (TOHM). 2012
12) Z.D. Zhou, et al. “The Roles of Amyloid Precursor Protein (APP) in Neurogenesis, Implications to Pathogenesis and Therapy of Alzheimer's Disease (AD)”. Cell Adhension & Migration. 2011 Jul 1;5(4):280-92.
13) Z.D. Zhou, et al. “Iron species-mediated dopamine oxidation, proteasome inhibition, and dopaminergic cell demise: implications for iron-related dopaminergic neuron degeneration.” Free Radical Biology & Medicine, 2010 Dec 15;49(12):1856-71.
14) Z.D. Zhou, et al. “Dopamine auto-oxidation aggravates non-apoptotic cell death induced by overexpression of human A53T mutant alpha-synuclein in dopaminergic PC12 cells”. Journal of Neurochemistry, 108 (2009) 601-610.
15) Z.D. Zhou, et al. “Dopamine-related and caspase-independent apoptosis in dopaminergic neurons induced by overexpression of human wild type or mutant α-synuclein,” Experimental Cell Research, 312 (2006) 156-170.
16) Z.D. Zhou, et al. “Notch as a Molecular Switch in Neural Stem Cells (NSC),” IUBMB life, 62 (2010), 618-623.
17) Z.D. Zhou & T.M. Lim, “Role of glutathione (GSH) on dopamine (DA) oxidation, studied by improved tandem HPLC procedures plus ESI-MS.” Neurochem Research, 34 (2009) 316-326.
18) Z.D. Zhou & T.M. Lim, “Glutathione conjugates with dopamine-derived quinones to form reactive or non-reactive glutathione-conjugates, implications to dopaminergic neuron degeneration.” Neurochem Research, 2010 Nov;35(11):1805-18.
19) Z.D. Zhou, et al. “Endogenous dopamine (DA) renders dopaminergic cells vulnerable to challenge of proteasome inhibitor MG132” Free Radical Research, 42 (2008) 456-466.
20) Z.D. Zhou, T.M. Lim, “Dopamine (DA) induced irreversible proteasome inhibition via DA derived quinones.” Free Radical Research, 43 (2009), 417-430.