中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (12): 2669-2670.doi: 10.4103/1673-5374.373714

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

钙渗透性AMPA受体:一个被低估的治疗脑部病变的药理目标

  

  • 出版日期:2023-12-15 发布日期:2023-06-14

Calcium-permeable AMPA receptors: an underestimated pharmacological target for the therapy of brain pathologies

Sergei G. Gaidin*, Artem M. Kosenkov*   

  1. Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”, Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino, Russia
  • Online:2023-12-15 Published:2023-06-14
  • Contact: Sergei G. Gaidin, PhD, ser-gajdin@yandex.ru; Artem M. Kosenkov, PhD, kosenckov406@yandex.ru.
  • Supported by:
    This work was supported by the Ministry of Science and Higher Education of the Russian Federation in the framework of state assignment of PSCBR RAS 075-01512-22-02 (122112800049-0) supervising (including funding control and distribution) and realized by SGG and AMK. 

摘要: https://orcid.org/0000-0003-4221-5344 (Sergei G. Gaidin)
https://orcid.org/0000-0001-9482-3398 (Artem M. Kosenkov)

Abstract: Excitotoxicity resulting from the accumulation of extracellular glutamate (the main excitatory neurotransmitter in the brain) is one of the main causes of neuronal death in various brain pathologies, including traumatic brain injury, epilepsy, stroke, and a number of neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. An acute increase in extracellular glutamate concentration leads to neuronal dysfunction accompanied by oxidative stress, calcium homeostasis failure, a drop in energy metabolism, and loss of plasma membrane integrity. However, despite a more than 30-year history of studying glutamate excitotoxicity, there are no safe and effective drugs that prevent cell death under these pathological conditions. Numerous promising neuroprotective compounds have been rejected in clinical trials due to low efficacy and/or side effects. N-methyl-D-aspartate receptors (NMDARs) are considered the main source of Ca2+ influx during excitotoxicity, so various NMDAR antagonists have been primarily tested. However, the paradigm of NMDAR-Ca2+-mediated excitotoxicity formulated in the 1990s has outlived itself in terms of pharmacological potential. In this regard, the researchers have focused on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), the antagonists of which also demonstrate neuroprotective effects in in vitro studies.