Liu, XY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,firstname.lastname@example.org
One hypothesis for the etiology of Parkinson's disease (PD) is that the formation of' proteinaceous inclusion, which is mainly composed of α-synuclein, may contribute to the selective loss of dopaminergic neurons, To further explore the role of α-synuclein in neurodegeneration of PD, we examined the possible effects of aggregated α-synuclein on the intracellular redox state, dopamine level, and cell death of SK-N-SH cells. Our present Studies show that α-synuclein aggregation gives rise to both elevated intracellular oxidative state and dopamine level in SK-N-SH cells. Moreover, α-synuclein aggregation results in a higher ratio of apoptosis population (55.8% &PLUSMN; SEM) in cells overexpressing α-synuclein aggregation. compared to their normal Control groups (8,0% + SEM), In contrast. coexpression of hsp70 with α-synuclein suppresses the oxidative state shift. restores the normal dopamine levels and blocks neuron cell loss. Therefore, our data provided one possible mechanism by which the α-synuclein aggregation may lead to the neurodegeneration in PD via regulating the level of cytoplasmic dopamine and then disturbing, the intracellular redox homeostasis. On the other hand, hsp70 can mitigate the degenerative effect conferred by α-synuclein, acting as a protective factor in treatment or PD. © 2005 Elsevier Inc. All rights reserved.
Yu, FR; Xu, HT; Zhuo, M; Sun, LY; Dong, AW; Liu, XY.Impairment of redox state and dopamine level induced by alpha-synuclein aggregation and the preventive effect of hsp70,BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2005,331(1):278-284