Alpha-synuclein overexpression negatively regulates insulin receptor substrate 1 by activating mTORC1/S6K1 signaling

- α-Syn overexpression upregulated IRS-1 serine and downregulated tyrosine phosphorylation, resulting in accelerated IRS-1 turnover and reduced insulin-Akt signaling in SK-N-SH cells.
- mTORC1/S6K1 activation directly mediated insulin-induced hyperphosphorylation of IRS-1 serine residues under α-Syn overexpression in SK-N-SH cells.
- PP2A may protect insulin signaling under α-Syn overexpression by reversing IRS-1 serine phosphorylation in SK-N-SH cells.
- α-Syn negatively regulated IRS-1 in α-Syn transgenic mice.