alpha-synuclein promotes mitochondrial deficit and oxidative stress

Abnormal accumulation of the presynaptic protein alpha-synuclein has recent ly been implicated in the pathogenesis of Alzheimer's and Parkinson's disea ses. Because neurodegeneration in these conditions might be associated with mitochondrial dysfunction and oxidative stress, the effects of alpha-synuc lein were investigated in a hypothalamic neuronal cell. line (GT1-7). alpha -Synuclein overexpression in these cells resulted in formation of alpha-syn uclein-immunopositive inclusion-like structures and mitochondrial alteratio ns accompanied by increased levels of free radicals and decreased secretion of gonadotropin-releasing hormone. These alterations were ameliorated by p retreatment with anti-oxidants such as vitamin E. Taken together these resu lts suggest that abnormal accumulation of alpha-synuclein could lead to mit ochondrial alterations that may result In oxidative stress and, eventually, cell death.