000325028_sm_supplement. Methods .pdf (454.94 kB)

Supplementary Material for: Direct Interaction of α-Synuclein and AKT Regulates IGF-1 Signaling: Implication of Parkinson Disease

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posted on 08.04.2011, 00:00 by Chung J.-Y., Lee S.-J., Lee S.-H., Jung Y.S., Ha N.-C., Seol W., Park B.-J.
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.

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