Centre for the Neurobiology of Stress, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
Cell Stress Chaperones. 2010 Sep;15(5):545-53. doi: 10.1007/s12192-009-0167-0. Epub 2010 Jan 19.
Human neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been termed "protein misfolding disorders." Upregulation of heat shock proteins that target misfolded aggregation-prone proteins has been proposed as a potential therapeutic strategy to counter neurodegenerative disorders. The heat shock protein 70 (HSP70) family is well characterized for its cytoprotective effects against cell death and has been implicated in neuroprotection by overexpression studies. HSP70 family members exhibit sequence and structural conservation. The significance of the multiplicity of HSP70 proteins is unknown. In this study, coimmunoprecipitation was employed to determine if association of HSP70 family members occurs, including Hsp70B' which is present in the human genome but not in mouse and rat. Heteromeric complexes of Hsp70B', Hsp70, and Hsc70 were detected in differentiated human SH-SY5Y neuronal cells. Hsp70B' also formed complexes with Hsp40 suggesting a common co-chaperone for HSP70 family members.
人类神经退行性疾病，如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症，被称为“蛋白质错误折叠疾病”。上调靶向错误折叠聚集倾向蛋白的热休克蛋白被认为是对抗神经退行性疾病的潜在治疗策略。热休克蛋白 70（HSP70）家族因其对细胞死亡的细胞保护作用而得到很好的描述，并通过过表达研究表明与神经保护有关。HSP70 家族成员表现出序列和结构的保守性。HSP70 蛋白多样性的意义尚不清楚。在这项研究中，我们采用共免疫沉淀来确定 HSP70 家族成员是否发生了关联，包括 Hsp70B'，它存在于人类基因组中，但不存在于小鼠和大鼠中。在分化的人 SH-SY5Y 神经元细胞中检测到 Hsp70B'、Hsp70 和 Hsc70 的异源三聚体复合物。Hsp70B'还与 Hsp40 形成复合物，提示 HSP70 家族成员有共同的共伴侣。
