title: Direct interaction of α-synuclein and AKT regulates IGF-1 signaling: implication of Parkinson disease.
abstract: 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.
authors.affiliation: Department of Molecular Biology, College of Natural Science, Pusan National University, Busan, Republic of Korea.
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Chung
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Lee
authors.forename: Youn Sang
authors.initials: YS
authors.lastname: Jung
authors.forename: Nam-Chul
authors.initials: NC
authors.lastname: Ha
authors.forename: Wongi
authors.initials: W
authors.lastname: Seol
authors.forename: Bum-Joon
authors.initials: BJ
authors.lastname: Park
mesh_terms: D002460:Cell Line; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010300:Parkinson Disease / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D007334:Insulin-Like Growth Factor I; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt