[Ca2+-regulated enzymes calpain and calcineurin in neurodegenerative processes and prospects for neuroprotective pharmacotherapy].

Q3 Medicine
V H Knaryan, F P Sarukhanyan
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引用次数: 0

Abstract

Calcium (Ca2+) and Ca2+-regulated enzymes calpain and calcineurin are the key molecules of signaling mechanisms in neurons and ensure the normal course of intracellular neurochemical and neurophysiological processes. The imbalance and increase in the intracellular level of Ca2+ correlates with the activation of calpain and calcineurin. Inactivation of endogenous inhibitors and/or absence of exogenous pharmacological inhibitors of these enzymes may induce a cascade of intracellular mechanisms that are detrimental to the structural integrity and functional activity of neurons. The interrelated processes of Ca2+ imbalance, dysregulation of calpain and calcineurin are directly related to the development of intracellular pathophysiological reactions leading to the degeneration and death of selective neuronal populations in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The review briefly presents the characteristics of calpain and calcineurin, their interrelated role in the neurodegeneration processes. Data on the efficiency of the exogenous inhibitors (in vivo, in vitro) point out the potential role of pharmacological regulation of calpain and calcineurin for neuroprotection.

[钙+调节酶钙蛋白酶和钙调磷酸酶在神经退行性过程和神经保护药物治疗的前景]。
钙(Ca2+)及其调控酶钙蛋白酶(calpain)和钙调磷酸酶(calcalineurin)是神经元信号传导机制的关键分子,保证细胞内神经化学和神经生理过程的正常进行。细胞内Ca2+水平的失衡和升高与钙蛋白酶和钙调磷酸酶的激活有关。内源性抑制剂失活和/或缺乏这些酶的外源性药理学抑制剂可能诱导细胞内机制的级联反应,这对神经元的结构完整性和功能活性是有害的。在神经退行性疾病如阿尔茨海默病和帕金森病中,Ca2+失衡、钙蛋白酶和钙调磷酸酶的失调等相关过程与细胞内病理生理反应的发展直接相关,导致选择性神经元群的退化和死亡。本文简要介绍了钙蛋白酶和钙调神经磷酸酶的特点,以及它们在神经退行性变过程中的相互作用。关于外源性抑制剂(体内和体外)效率的数据指出了calpain和calcineurin在神经保护方面的潜在药理调节作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova Medicine-Psychiatry and Mental Health
CiteScore
0.80
自引率
0.00%
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0
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