Research: Parkinson’s Disease


 

Parkinson’s disease is the second most common neurodegenerative disorder and affects one in 100 individuals over the age of 50. Currently there are over 2 million PD patients in US. PD is clinically characterized by resting tremor, muscular rigidity, bradykinesia, and postural instability. The pathological hallmark of PD is degeneration of dopaminergic (DA) neurons in the substantia nigra. The causes of the vast majority of PD cases remain unknown but are thought to involve both genetic and environmental factors. A subset of familial cases of PD have been shown to be caused by genetic mutations. Our laboratory is interested in developing genetic models for the familial forms of PD, and we use these models to study pathogenic mechanisms underlying the disease. Such studies may provide valuable clues on pathogenesis of the more common sporadic form of PD.

 

The Yang lab has developed novel mouse models to study PD. DAT-Parkin-Q311X mice selectively express truncated mutant Parkin in dopaminergic neurons. This model develops PD-like phenotypes, including late-onset hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of aggregated alpha-synuclein. The lab also developed BAC-aSyn and BAC-aSyn1-120 mice that overexpress human alpha synuclein (aSyn), a gene underlying both genetic and sporadic forms of PD. These models overexpress either wildtype or c-terminal truncated human aSyn using human BAC transgenes and are Cre/LoxP conditional, similar to BACHD, making them extremely valuable for dissecting cell-type-specific contributions to PD pathogenesis. Preliminary study suggests that BAC-aSyn1-120 mice may exhibit age-dependent Lewy Neurite pathology similar to PD.

 


 

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