Direct Interaction of alpha-Synuclein and AKT Regulates IGF-1 Signaling: Implication of Parkinson Disease

초록

Genetic mutation of alpha-synuclein (alpha-SYN) is clearly verified as the causal factor of human and mouse Parkinson's disease. However, biological function of alpha-SYN has not been clearly demonstrated until now. In this investigation, we reveal that alpha-SYN is a co-regulator of growth factor-induced AKT activation. Elimination of SYN reduces the IGF-1-mediated AKT activation. Similarly, mutant SYN suppresses the IGF-1-induced AKT activation. Wild-type SYN can interact with AKT and enhance the solubility and plasma localization of AKT in response to IGF-1, whereas mutant alpha-SYNs do not interact with AKT. In addition, elevated expression of SYN blocks the AKT activation. We also find that si-RNA against alpha-SYN abolished the protective effect of IGF-1 against DNA damage-induced apoptosis. Our result strongly indicates that Parkinson's disease, induced by alpha-SYN mutation, is evoked by deregulation of the AKT-signaling cascade. Copyright (C) 2011 S. Karger AG, Basel

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