RETRACTED: α‐Synuclein regulates neuronal survival via Bcl‐2 family expression and PI3/Akt kinase pathway

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Abstract
α‐Synuclein (α‐SN) is a ubiquitous protein that is especially abundant in the brain and has been postulated to play a central role in the pathogenesis of Parkinson's disease, Alzheimer's disease, and other neurodegenerative disorders. However, little is known about the neuronal functions of α‐SN and the molecular and cellular mechanisms underlying neuronal loss. Here, we show that α‐SN plays dual roles of neuroprotection and neurotoxicity depending on its concentration or level of expression. At nanomolar concentrations, α‐SN protected neurons against serum deprivation, oxidative stress, and excitotoxicity through the PI3/Akt signaling pathway, and its protective effect was increased by Bcl‐2 overexpression. Conversely, at both low micromolar and overexpressed levels in the cell, α‐SN resulted in cytotoxicity. This might be related to decreased Bcl‐xL expression and increased bax expression, which is subsequently followed by cytochrome c release and caspase activation and also by microglia‐mediated inflammatory responses via the NFκB and mitogen‐activated protein kinase pathways.
Funding Information
  • Ministry of Science and Technology