University of California, San Francisco (UCSF)

Alpha-Synuclein Expression and Aging in C. Elegans

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As the world’s population ages, neurodegenerative diseases have become increasingly important causes of morbidity and mortality. Aggregation of proteins such as alpha-synuclein in Parkinson’s Disease (PD) and A beta and tau in Alzheimer’s Disease represent a common pathophysiological feature. Despite this similarity, these diseases affect very different neuronal populations. Understanding selective vulnerability of neurons to toxic proteins is fundamental to developing treatments to diseases of aging.

I hope to better understand selective neuronal vulnerability by testing the hypothesis that neurons affected by alpha-synuclein have a genetic expression profile that promotes alpha-synuclein toxicity. Preliminary studies using a C. elegans model of PD have shown that expressing alpha-synuclein in neurons causes an age- and concentration-dependent change in the animal’s health and mobility. I will first determine the temporal order in which neurons are affected by alpha-synuclein expression and their common characteristics will be demonstrated. I next will focus on testing factors previously identified to affect selective vulnerability to alpha-synuclein and performing an unbiased screen to discover novel factors. Finally, the mechanisms by which these molecules promote selective neuronal will be investigated.

Few persons in society have not felt the impact of neurodegenerative diseases. Finding cures for these diseases would relieve a tremendous burden of human suffering and save this country’s health care system millions of dollars. Understanding why certain neurons are affected early in PD would be a major step towards unraveling how these diseases develop and ultimately finding a cure.