alpha-synuclein promotes mitochondrial deficit and oxidative stress.
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.
Departments of Pathology, Neurosciences, and Reproductive Medicine, the University of California at San Diego, La Jolla, California, USA.
L J
LJ
Hsu
Y
Y
Sagara
A
A
Arroyo
E
E
Rockenstein
A
A
Sisk
M
M
Mallory
J
J
Wong
T
T
Takenouchi
M
M
Hashimoto
E
E
Masliah
D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D005978:Glutathione / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051843:Synucleins; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein; D007987:Gonadotropin-Releasing Hormone; D005978:Glutathione