Chung Ji-Yun, Lee Su-Jin, Lee Sun-Hye, Jung Youn Sang, Ha Nam-Chul, Seol Wongi, Park Bum-Joon
Department of Molecular Biology, College of Natural Science, Pusan National University, Busan, Republic of Korea.
Neurosignals. 2011;19(2):86-96. doi: 10.1159/000325028. Epub 2011 Apr 8.
Genetic mutation of α-synuclein (α-SYN) is clearly verified as the causal factor of human and mouse Parkinson's disease. However, biological function of α-SYN has not been clearly demonstrated until now. In this investigation, we reveal that α-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 α-SYNs do not interact with AKT. In addition, elevated expression of SYN blocks the AKT activation. We also find that si-RNA against α-SYN abolished the protective effect of IGF-1 against DNA damage-induced apoptosis. Our result strongly indicates that Parkinson's disease, induced by α-SYN mutation, is evoked by deregulation of the AKT-signaling cascade.
