Induction of heat shock proteins in differentiated human and rodent neurons by celastrol
Induction of heat shock proteins in differentiated human and rodent neurons by celastrol
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DOI：
10.1379/csc-269.1
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发表时间：
2007-09-01
影响因子：
3.8
通讯作者：
Brown, Ian R.
中科院分区：
文献类型：
--
作者：
Chow, Ari M.;Brown, Ian R.
神经退行性疾病如阿尔茨海默病、帕金森病和肌萎缩性侧索硬化症被称为蛋白质错误折叠疾病，其特征在于蛋白质聚集体的神经元积累。涉及诱导分化的神经元中的热休克蛋白（Hsps）的细胞应激反应的操纵提供了一种治疗策略，以对抗神经元蛋白的构象变化，其触发导致神经退行性疾病的致病性级联反应。热休克蛋白是蛋白质修复剂，提供了一条防线，对错误折叠，聚集倾向的蛋白质。这些蛋白质在分化的神经元中不被常规的热休克诱导。我们已经发现，与培养的啮齿动物神经元细胞相比，雷公藤红素（一种奎宁甲基化物三萜）在组织培养物中生长的分化的人神经元中诱导更广泛的一组Hsps（包括Hsp70 B ′）的表达。因此，雷公藤红素对人类神经退行性疾病的有益作用可能超过其在这些疾病的啮齿动物模型中的潜力。
Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been termed protein misfolding disorders that are characterized by the neuronal accumulation of protein aggregates. Manipulation of the cellular stress-response involving induction of heat shock proteins (Hsps) in differentiated neurons offers a therapeutic strategy to counter conformational changes in neuronal proteins that trigger pathogenic cascades resulting in neurodegenerative diseases. Hsps are protein repair agents that provide a line of defense against misfolded, aggregation-prone proteins. These proteins are not induced in differentiated neurons by conventional heat shock. We have found that celastrol, a quinine methide triterpene, induced expression of a wider set of Hsps, including Hsp70B', in differentiated human neurons grown in tissue culture compared to cultured rodent neuronal cells. Hence the beneficial effect of celastrol against human neurodegenerative diseases may exceed its potential in rodent models of these diseases.