Rescue of alpha-synuclein cytotoxicity by insulin-like growth factors.
While mutation of alpha-synuclein is a cause of autosomal-dominant Parkinson's disease (PD), it is still elusive as to how alpha-synuclein is involved in the pathogenesis of PD. Here, we show that dopamine-dependent accumulation of alpha-synuclein in cultured cells results in apoptosis. Furthermore, activation of insulin-like growth factor 1 (IGF-1) pathway can rescue alpha-synuclein toxicity and suppress alpha-synuclein aggregation through the activation of PI3K/Akt pathways. These results suggest the therapeutic potential of IGF-1 pathway in Parkinson disease.
Kao
Shyan-Yuan
SY
Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA. shyan-yuan_kao@meei.harvard.edu
D017209:Apoptosis; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
D051844:alpha-Synuclein; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D004298:Dopamine