Heat shock response and insulin-associated neurodegeneration.

Heat shock response and insulin-associated neurodegeneration.
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DOI:
10.1016/j.tips.2011.11.001
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发表时间:
2012-03
影响因子:
13.8
通讯作者:
Blagg BS
Blagg BS
中科院分区:
医学1区
文献类型:
--
作者:
Urban MJ;Dobrowsky RT;Blagg BS

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功能失调的胰岛素和胰岛素样生长因子-I(IGF-I)信号传导有助于糖尿病、糖尿病性周围神经病变(DPN)、阿尔茨海默病(AD)、帕金森病(PD)和亨廷顿病(HD)的病理进展。尽管其普遍存在,但可用于治疗这些神经退行性疾病的治疗选择有限。因此,建立胰岛素/IGF-I和这些疾病的病因之间的联系,可能会提供替代方法对他们的管理。许多热休克蛋白(Hsps)是众所周知的分子伴侣,可以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,调节热休克蛋白可能是一个有前途的治疗途径,改善胰岛素和IGF-I信号。热休克反应(HSR)的药理学诱导可能与胰岛素/IGF-I信号传导交叉,以改善神经退行性表型的各个方面。在此,我们审查之间的交集热休克蛋白和胰岛素/IGF系统在正常和病理条件下。讨论将强调无毒的HSR诱导剂作为可行的治疗剂的潜力。
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.
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