期刊
NEUROBIOLOGY OF DISEASE
卷 21, 期 2, 页码 421-430出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2005.08.003
关键词
apoptosis; heat shock protein; HMG-CoA reductase inhibitors; neurodegeneration; neuroprotection; PI3K/Akt; retina; statins
Heat shock proteins (Hsps) are stress proteins that mediate protein stabilization in various tissues and protect cells from environmental stress. Novel evidence suggests that overexpression of the small heat shock protein 27 (Hsp27) in neurons protects against neurotoxic stimuli and may act as an inhibitor of neurodegeneration. Overexpression of Hsps has been achieved by different means including pharmacological induction. Here, we show that intravitreal injection of the 3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor simvastatin induces Hsp27 expression in axotomized retinal ganglion cells (RGCs) and enhances RGC survival 7 and 14 days after optic nerve (ON) axotomy by 90% and 19%, respectively. The flavonoid quercetin inhibited Hsp27 induction and abrogated simvastatin-mediated neuroprotection. Simvastatin increased Akt phosphorylation in vivo, indicating that the PI3K/Akt pathway contributes to central nervous system (CNS) protective effects achieved. We propose the use of statins as a feasible approach to reduce lesion-induced CNS neuronal degeneration in vivo. (c) 2005 Elsevier Inc. All rights reserved.
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