Abstract

Glutamate (Glu) excitotoxicity, which accompanies brain ischemia or traumatic brain injury, is the leading mechanism of neuronal death. In the present work, we studied the effects of the peptides HFRWPGP (ACTH_6–9PGP), KKRRPG, and PyrRP on the survival of cultured cortical neurons on the background of excitotoxic effect of Glu (100 µM). Biochemical (MTT/WST) and morphometric analyzes showed that, depending on the dose, ACTH_6–9PGP and KKRRPGP protect neurons from the cells death, while PyrRP, conversely, enhances it. The neuroprotective effect of ACTH_6–9PGP is accompanied by a slowdown in the development of delayed calcium dysregulation and synchronous mitochondrial depolarization. Among the studied peptides, only ACTH_6–9PGP significantly increased the number of neurons that restored Ca²⁺ homeostasis after Glu was abolished. The influence of KKRRPGP was less pronounced, whereas PyrRP, on the contrary, reduced the number of neurons with low [Ca²⁺]_i. Thus, this study revealed the high therapeutic significance of ACTH_6–9PGP and allowed assessing the prospects for its possible clinical use.

中文翻译：

---

谷氨酸兴奋性毒性时，培养的皮质神经元中的肽HFRWPGP（ACTH6-9PGP），KKRRPGP和PyrRP的神经保护潜能。

摘要

谷氨酸（Glu）的兴奋性毒性伴随着脑缺血或外伤性脑损伤，是神经元死亡的主要机制。在当前的工作中，我们研究了肽HFRWPGP（ACTH _6-9 PGP），KKRRPG和PyrRP对Glu（100 µM）的兴奋毒性作用背景下培养的皮质神经元存活的影响。生化（MTT / WST）和形态分析表明，取决于剂量，ACTH _6–9 PGP和KKRRPGP可以保护神经元免受细胞死亡，而PyrRP则可以增强神经元的死亡。ACTH _6–9 PGP的神经保护作用伴随着钙延迟失调和线粒体同步去极化的发展减慢。在研究的肽中，只有ACTH _6–9在Glu取消后，PGP显着增加了恢复Ca ²⁺稳态的神经元数量。KKRRPGP的影响不太明显，而PyrRP则减少了[Ca ²⁺ ] _i低的神经元的数量。因此，这项研究揭示了ACTH _6-9 PGP的高治疗意义，并允许评估其可能的临床应用前景。