Laboratory of Molecular Neurobiology, Academy of Biology and Biotechnology, Southern Federal University, 344090 Rostov-on-Don, Russia.
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Cells. 2021 Dec 29;11(1):93. doi: 10.3390/cells11010093.
The search for effective neuroprotective agents for the treatment of neurotrauma has always been of great interest to researchers around the world. Extracellular heat shock protein 70 (eHsp70) is considered a promising agent to study, as it has been demonstrated to exert a significant neuroprotective activity against various neurodegenerative diseases. We showed that eHsp70 can penetrate neurons and glial cells when added to the incubation medium, and can accumulate in the nuclei of neurons and satellite glial cells after axotomy. eHsp70 reduces apoptosis and necrosis of the glial cells, but not the neurons. At the same time, co-localization of eHsp70 with p53 protein, one of the key regulators of apoptosis, was noted. eHsp70 reduces the level of the p53 protein apoptosis promoter both in glial cells and in the nuclei and cytoplasm of neurons, which indicates its neuroprotective effect. The ability of eHsp70 to reverse the proapoptotic effect of the p53 activator WR1065 may indicate its ability to regulate p53 activity or its proteosome-dependent degradation.
寻找有效的神经保护剂来治疗神经创伤一直是全世界研究人员关注的焦点。细胞外热休克蛋白 70(eHsp70)被认为是一种很有前途的研究药物,因为它已被证明对各种神经退行性疾病具有显著的神经保护活性。我们发现,当添加到孵育培养基中时,eHsp70 可以穿透神经元和神经胶质细胞,并在轴突切断后积累在神经元和卫星神经胶质细胞的核内。eHsp70 减少了神经胶质细胞的凋亡和坏死,但对神经元没有影响。同时,还注意到 eHsp70 与 p53 蛋白(凋亡的关键调节剂之一)共定位。eHsp70 降低了 p53 蛋白凋亡促进剂在神经胶质细胞以及神经元的核和细胞质中的水平,这表明其具有神经保护作用。eHsp70 逆转 p53 激活剂 WR1065 的促凋亡作用的能力可能表明其能够调节 p53 活性或其蛋白酶体依赖性降解。