Neuroscience Graduate Program, The University of Kansas, Lawrence, KS 66045, USA.
Trends Pharmacol Sci. 2012 Mar;33(3):129-37. doi: 10.1016/j.tips.2011.11.001. Epub 2011 Dec 13.
Dysfunctional insulin and insulin-like growth factor-I (IGF-I) signaling contributes to the pathological progression of diabetes, diabetic peripheral neuropathy (DPN), Alzheimer's (AD), Parkinson's (PD) and Huntington's diseases (HD). Despite their prevalence, there are limited therapeutic options available for the treatment of these neurodegenerative disorders. Therefore, establishing a link between insulin/IGF-I and the pathoetiology of these diseases may provide alternative approaches toward their management. Many of the heat shock proteins (Hsps) are well-known molecular chaperones that solubilize and clear damaged proteins and protein aggregates. Recent studies suggest that modulating Hsps may represent a promising therapeutic avenue for improving insulin and IGF-I signaling. Pharmacological induction of the heat shock response (HSR) may intersect with insulin/IGF-I signaling to improve aspects of neurodegenerative phenotypes. Herein, we review the intersection between Hsps and the insulin/IGF systems under normal and pathological conditions. The discussion will emphasize the potential of non-toxic HSR inducers as viable therapeutic agents.
胰岛素和胰岛素样生长因子-I（IGF-I）信号功能障碍导致糖尿病、糖尿病周围神经病变（DPN）、阿尔茨海默病（AD）、帕金森病（PD）和亨廷顿病（HD）等神经退行性疾病的病理进展。尽管这些疾病很常见，但目前针对这些神经退行性疾病的治疗选择有限。因此，在胰岛素/IGF-I 与这些疾病的发病机制之间建立联系，可能为其治疗提供替代方法。许多热休克蛋白（Hsps）是众所周知的分子伴侣，可溶解和清除受损的蛋白质和蛋白质聚集体。最近的研究表明，调节 Hsps 可能是改善胰岛素和 IGF-I 信号的有前途的治疗途径。热休克反应（HSR）的药理学诱导可能与胰岛素/IGF-I 信号交叉，以改善神经退行性表型的各个方面。本文综述了正常和病理条件下 Hsps 与胰岛素/IGF 系统之间的交叉。讨论将强调无毒 HSR 诱导剂作为可行的治疗剂的潜力。
