|Department Affiliations||Department of Psychiatry and Behavioral Sciences, Division of Neurobiology|
|SOM Address||8-121 CMSC|
Our research program focuses on understanding the pathogenesis, molecular mechanisms and developing experimental therapeutics of neurodegenerative diseases, particular Huntington’s disease (HD) and Parkinson’s disease (PD).
A multifaceted array of experimental models of neurodegenerative disorders is being employed in our laboratory in order to establish the molecular and cellular changes that occur in neurological disorders. Data obtained in these experimental models are integrated with data obtained in therapeutic trial studies to determine why neuronal dysfunction and degeneration occur in the disorders. In addition to identifying the molecular and cellular alterations that lead to neuronal degeneration, the research projects in our laboratory focus on discovering new therapeutic targets and developing biomarkers for these neurodegenerative diseases. A major effort is underway to determine the effects of energy metabolism and brain aging on neurodegeneration. Interestingly, several molecules that can be upregulated by dietary restriction are neuroprotective in the models of neurodegenerative diseases, suggesting a mechanism whereby dietary factors and drugs affecting energy metabolism and brain aging may modify the onset and progression of neurodegenerative disorders.
Our research goals are: (1) understanding the pathogenesis and cell death pathway to reveal potential targets for therapeutic intervention. We are investigating the alteration and contribution of microRNA in pathogenesis of HD and PD; (2) investigating endogenous survival pathways and inducing these pathways to restore full function or replace lost neurons in neurodegenerative diseases. We are examining role of neurotrophic factors and neuronal sirtuins in neurodegeneration; (3) screening and discovering new potent neuroprotective compounds in models of HD and PD. We utilize cell models of HD and PD to screen available compounds libraries to discover potential neuroprotective compounds; (4) preclinical trials of new candidate compounds in transgenic mouse models of neurodegenerative disorders. We are examining the potential neuroprotective compounds and approaches in animal models of HD and PD. (5) developing and validating biomarkers to evaluate therapeutics. We are using structure MRI to detect the onset and progression of brain atrophy in selective brain regions and use MRI measure as a biomarker to evaluate therapeutics longitudinally.
- Jiang M, Peng Q, Liu X, Jin J, Hou Z, Zhang J, Mori S, Ross CA, Ye K and Duan W. Small molecule TrkB receptor agonists improve motor function and extend survival in a mouse model of Huntington’s disease. Hum Mol Genet 2013, 22(12):2462-2470.
- Jin J, Albertz J, Guo Z, Peng Q, Rudow G, Troncoso JC, Ross CA, Duan W. Neuroprotective effects of PPAR-γ agonist rosiglitazone in N171-82Q mouse model of Huntington’s disease. J Neurochem, 2013,125(3):410-419.
- Duan W. Sirtuins: from metabolic regulation to brain aging. Frontiers in Aging Neuroscience 2013, 5(36): 1-13.
- Duan W. Targeting sirtuin-1 in Huntington’s disease: rationale and current status. CNS Drugs 2013, 27(5):345-352.
- Fu J, Jin J, Cichewicz RH, Hageman SA, Ellis TK, Xiang L, Peng Q, Jiang M, Arbez N, Hotaling K, Ross CA and Duan W. Trans-(-)-ε-viniferin increases mitochondrial sirtuin 3 (SIRT3), activates AMPK, and protects cells in models of Huntington’s disease. J. Bio Chem, 2012, 287(29):24460-72.
- Jin J, Cheng Y, Zhang Y, Wood W, Peng Q, Hutchison E, Mattson MP, Becker KG, Duan W. Interrogation of brain miRNA and mRNA expression profiles reveals a molecular regulatory network that is perturbed by mutant huntingtin. J Neurochem, 2012, 123(4): 477-90.
- Jiang M, Wang J, Fu J, Du L, Jeong H, West T, Xiang L, Peng Q, Hou Z, Cai H, Seredenin T, Arbez N, Zhu S, Sommers K, Qian J, Zhang J, Mori S, Yang XW, Tamashiro KLK, Aja S, Moran TH, Luthi-Carter R, Martin B, Maudsley S, Mattson MP, Cichewicz RH, Ross CA, Holtzman DM, Krainc D, Duan W. Neuroprotective role of Sirt1 in mammalian models of Huntington’s disease through activation of multiple Sirt1 targets. Nature Medicine, 2011, 18(1): 153-158.
- Cheng Y, Peng Q, Hou Z, Aggarwal M, Zhang J, Mori S, Ross CA, Duan W. Structural MRI detects progressive regional brain atrophy and neuroprotective effects in N171-82Q Huntington’s disease mouse model. Neuroimage, 2011, 56:1027-1034.
- Jiang M, Porat-Shliom Y, Pei Z, Cheng Y, Xiang L, Sommers K, Li Q, Gillardon F, Hengerer B, Berlinicke C, Smith WW, Zack D, Poirier MA, Ross CA, Duan W. Baicalein reduces E46K alpha-synuclein aggregation in vitro and protects cells against E46K alpha-synuclein toxicity in cell models of familiar Parkinsonism. J Neurochem, 2010, 114(2):419-29.
- Zhang J, Peng Q, Li Q, Jahanshad N, Hou Z, Jiang M, Masuda N, Langbehn DR, Miller MI, Mori S, Ross CA, Duan W. Longitudinal characterization of brain atrophy of a Huntington’s disease mouse model by automated morphological analyses of magnetic resonance images. Neuroimage, 2010, 49(3):2340-51.
- Duan W, Ross CA. Potential therapeutic targets for neurodegenerative diseases: lessons learned from calorie restriction. Current Drug Target 2010, 11(10):1281-92.