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丹曲林在神经退行性疾病中的神经保护作用:抑制病理性炎症的作用

Neuroprotective effects of dantrolene in neurodegenerative disease: Role of inhibition of pathological inflammation.

作者信息

Zhang Wenjia, Zhao Xu, Bhuiyan Piplu, Liu Henry, Wei Huafeng

机构信息

Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Department of Anesthesiology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, Shandong 250021, China.

出版信息

J Anesth Transl Med. 2024 Jun;3(2):27-35. doi: 10.1016/j.jatmed.2024.04.002. Epub 2024 Apr 30.

Abstract

Neurodegenerative diseases (NDs) refer to a group of diseases in which slow, continuous cell death is the main pathogenic event in the nervous system. Most NDs are characterized by cognitive dysfunction or progressive motor dysfunction. Treatments of NDs mainly target alleviating symptoms, and most NDs do not have disease-modifying drugs. The pathogenesis of NDs involves inflammation and apoptosis mediated by mitochondrial dysfunction. Dantrolene, approved by the US Food and Drug Administration, acts as a RyRs antagonist for the treatment of malignant hyperthermia, spasticity, neuroleptic syndrome, ecstasy intoxication and exertional heat stroke with tolerable side effects. Recently, dantrolene has also shown therapeutic effects in some NDs. Its neuroprotective mechanisms include the reduction of excitotoxicity, apoptosis and neuroinflammation. In summary, dantrolene can be considered as a potential therapeutic candidate for NDs.

摘要

神经退行性疾病(NDs)是指一类以神经系统中缓慢、持续的细胞死亡为主要致病事件的疾病。大多数神经退行性疾病的特征是认知功能障碍或进行性运动功能障碍。神经退行性疾病的治疗主要针对缓解症状,并且大多数神经退行性疾病没有疾病修饰药物。神经退行性疾病的发病机制涉及由线粒体功能障碍介导的炎症和细胞凋亡。经美国食品药品监督管理局批准的丹曲林,作为一种兰尼碱受体(RyRs)拮抗剂,用于治疗恶性高热、痉挛、抗精神病药综合征、摇头丸中毒和劳力性热射病,副作用可耐受。最近,丹曲林在一些神经退行性疾病中也显示出治疗效果。其神经保护机制包括减少兴奋性毒性、细胞凋亡和神经炎症。总之,丹曲林可被视为神经退行性疾病的潜在治疗候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75b3/11138240/39afe629e7ad/nihms-1995558-f0001.jpg

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