{"title":"Calpain Mediated Neurodegeneration in Parkinson’s disease","authors":"V. H. Knaryan","doi":"10.1134/s1819712423040116","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p> Parkinson’s disease (PD), a neurodegenerative movement disorder, is clinically manifested by disturbances in motor functions and non-motor symptoms, caused by progressive degeneration of nigrostriatal dopaminergic neurons and neurons in selected areas of the central and peripheral nervous system. The multifaceted pathogenesis of PD is associated with sustained mitochondrial dysfunction, oxidative stress, aberrant Са<sup>2+</sup> homeostasis, which contribute to the activation of Са<sup>2+</sup>-dependent protease calpain. Calpain plays role in neuronal signaling mechanisms, ensuring the normal course of intracellular neurochemical and neurophysiological processes. In neuropathological conditions, elevation of intracellular Ca<sup>2+</sup> and calpain activation, downregulation of endogenous and/or absence of exogenous pharmacological inhibitors of calpain, instigate calpain-mediated activation of apoptotic pathways, leading to degeneration and loss of selectively vulnerable nigrostriatal dopaminergic neurons in the brain. We have shown that at experimental (in vivo, in vitro) and human (<i>postmortem</i>) PD dorsal neurons and ventral motoneurons of the spinal cord are also affected through the calpain-mediated mechanisms of neurodegeneration. Synthetic calpain inhibitors – calpeptin, SNJ1945, and SJA6017, exhibited neuroprotective effects in the brain and spinal cord (in vivo, in vitro), suggesting calpain as a prospective target molecule for pharmacological therapy in the brain and spinal cord at PD<i>.</i></p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":null,"pages":null},"PeriodicalIF":0.5000,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1134/s1819712423040116","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Parkinson’s disease (PD), a neurodegenerative movement disorder, is clinically manifested by disturbances in motor functions and non-motor symptoms, caused by progressive degeneration of nigrostriatal dopaminergic neurons and neurons in selected areas of the central and peripheral nervous system. The multifaceted pathogenesis of PD is associated with sustained mitochondrial dysfunction, oxidative stress, aberrant Са2+ homeostasis, which contribute to the activation of Са2+-dependent protease calpain. Calpain plays role in neuronal signaling mechanisms, ensuring the normal course of intracellular neurochemical and neurophysiological processes. In neuropathological conditions, elevation of intracellular Ca2+ and calpain activation, downregulation of endogenous and/or absence of exogenous pharmacological inhibitors of calpain, instigate calpain-mediated activation of apoptotic pathways, leading to degeneration and loss of selectively vulnerable nigrostriatal dopaminergic neurons in the brain. We have shown that at experimental (in vivo, in vitro) and human (postmortem) PD dorsal neurons and ventral motoneurons of the spinal cord are also affected through the calpain-mediated mechanisms of neurodegeneration. Synthetic calpain inhibitors – calpeptin, SNJ1945, and SJA6017, exhibited neuroprotective effects in the brain and spinal cord (in vivo, in vitro), suggesting calpain as a prospective target molecule for pharmacological therapy in the brain and spinal cord at PD.
期刊介绍：
Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components.
The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.
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