Alpha-synuclein is a presynaptic
protein which is implicated in some
neurodegenerative disorders including
Parkinson's disease,
dementia with Lewy bodies, multiple systems
atrophy, and
Hallervorden-Spatz disease, and its overexpression contributes to the loss of dopaminergic neurons. Although the role of
alpha-synuclein in these paradigms has been widely documented, its exact function is still elusive. And the dysfunction of the
transcription factor nuclear factor (
NF-kappaB) also exists in many
neurodegenerative diseases. In this reason the purpose of this study was to investigate the molecular mechanism of
alpha-synuclein's toxicity and its association with
NF-kappaB by MTT assay, Western blot method, and
luciferase assay. Results showed that overexpressed
alpha-synuclein and
1-methyl-4-phenylpyridinium (MPP(+)) suppressed the SH-SY5Y cell viability and attenuate
NF-kappaB-mediated
luciferase expression significantly. Moreover, the impairment function was enhanced with the increase of
alpha-synuclein protein level. We also found that overexpressed
alpha-synuclein localized both in the cytoplasms and nuclei, down-regulated the anti-apoptotic Bcl-2 expression and up-regulated the pro-apoptotic
glycogen synthase kinase 3beta (
GSK3beta)
protein level. In conclusion, all these findings mentioned above suggested that
alpha-synuclein shared some toxic functional homology with
neurotoxin MPP(+), and the proapoptotic effects of
alpha-synuclein might be mediated at least in part by the impairment of
NF-kappaB signaling pathway which involves
GSK3beta.