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(American Journal of Pathology. 2000;157:401-410.)
© 2000 American Society for Investigative Pathology

Regular Articles

{alpha}-Synuclein Promotes Mitochondrial Deficit and Oxidative Stress

Leigh J. Hsu*{dagger}, Yutaka Sagara{dagger}, Armando Arroyo{ddagger}, Edward Rockenstein{dagger}, Abbyann Sisk{dagger}, Margaret Mallory{dagger}, Jeff Wong{ddagger}, Takato Takenouchi{dagger}, Makoto Hashimoto{dagger} and Eliezer Masliah*{dagger}

From the Departments of Pathology,*
Neurosciences,{dagger}
and Reproductive Medicine,{ddagger}
the University of California at San Diego, La Jolla, California

Abnormal accumulation of the presynaptic protein {alpha}-synuclein has recently been implicated in the pathogenesis of Alzheimer’s and Parkinson’s diseases. Because neurodegeneration in these conditions might be associated with mitochondrial dysfunction and oxidative stress, the effects of {alpha}-synuclein were investigated in a hypothalamic neuronal cell line (GT1-7). {alpha}-Synuclein overexpression in these cells resulted in formation of {alpha}-synuclein-immunopositive inclusion-like structures and mitochondrial alterations accompanied by increased levels of free radicals and decreased secretion of gonadotropin-releasing hormone. These alterations were ameliorated by pretreatment with anti-oxidants such as vitamin E. Taken together these results suggest that abnormal accumulation of {alpha}-synuclein could lead to mitochondrial alterations that may result in oxidative stress and, eventually, cell death.




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