Dedeoglu Alpaslan, Ferrante Robert J, Andreassen Ole A, Dillmann Wolfgang H, Beal M Flint
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
Exp Neurol. 2002 Jul;176(1):262-5. doi: 10.1006/exnr.2002.7933.
Heat shock proteins (HSPs) are induced in response to oxidative stress, hypoxia-ischemia, and neuronal injury and play a protective role. Malonate and 3-nitropropionic acid (3-NP) are well-characterized animal models of Huntington's Disease (HD). They inhibit succinate dehydrogenase, inducing mitochondrial dysfunction, which triggers the generation of superoxide radicals, secondary excitotoxicity, and apoptosis. In this study, we examined whether the 70-kDa heat shock protein (HSP-70) is protective against neurotoxicity induced by malonate and 3-NP. Homozygous and heterozygous HSP-70 overexpressing mice (HSP-70+/+, HSP-70+/-) and wild-type controls received 3-NP or malonate and striatal lesion sizes were evaluated by stereology. Compared to HSP-70+/+ and HSP-70+/-, wild-type controls showed significantly larger striatal lesions following 3-NP or malonate injections. These findings support the idea that HSP-70 has a neuroprotective role that may be useful in the treatment of neurodegenerative diseases.
热休克蛋白（HSPs）在氧化应激、缺氧缺血和神经元损伤时被诱导产生，并发挥保护作用。丙二酸和3-硝基丙酸（3-NP）是亨廷顿舞蹈病（HD）典型的动物模型。它们抑制琥珀酸脱氢酶，导致线粒体功能障碍，进而引发超氧自由基的产生、继发性兴奋性毒性和细胞凋亡。在本研究中，我们检测了70-kDa热休克蛋白（HSP-70）是否对丙二酸和3-NP诱导的神经毒性具有保护作用。同型和异型HSP-70过表达小鼠（HSP-70+/+、HSP-70+/-）以及野生型对照接受3-NP或丙二酸处理，通过体视学评估纹状体损伤大小。与HSP-70+/+和HSP-70+/-相比，野生型对照在注射3-NP或丙二酸后纹状体损伤明显更大。这些发现支持了HSP-70具有神经保护作用的观点，这可能对神经退行性疾病的治疗有用。
