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2005/2U - Abstract

Grant Information

Grant
2005/2U
Aging - Fellowship
Title
The Real Time Analysis of Synuclein Multimers in Live Cells
Investigator
Ken Nakamura, MD, PhD
Institution
UCSF
Department of Neurology
Funding Status
  • Completed
  • 3 years, $60,000 per year
  • 7/1/2005 to 6/30/2008

Abstract

2005/2U - Abstract
Brief Summary
"The Real Time Analysis of Synuclein Multimers in Live Cells"

Parkinson’s disease (PD) is a common and debilitating neurodegenerative disorder with no known cure. The protein alpha-synuclein plays a central role in the pathogenesis of PD, although little is known about the mechanisms by which alpha-synuclein influences PD, or about its normal function. alpha-Synuclein is known to undergo major and distinct conformational changes when it binds synthetic lipids or when it forms inclusions in test tubes. These conformational changes are widely presumed to be central to the normal and pathogenic functions of alpha-synuclein. However, it has not previously been possible to assess the conformation of alpha-synuclein in a physiologically relevant context, before it forms morphologically recognizable aggregates. To address this, we have designed fluorescent reporters for the conformation of alpha-synuclein, and used these to characterize the conformation and multimerization of alpha-synuclein in test tubes and in living cells. We have also used these reporters to compare the binding of alpha-synuclein to various cellular membranes, and found that alpha-synuclein has a selective affinity for mitochondria, an organelle widely implicated in the pathogenesis of PD. My current efforts are directed at characterizing the mechanism by which alpha-synuclein binds to mitochondria, as well as the functional consequences of this interaction.

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