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治疗运动障碍的正确轨道:帕金森病和亨廷顿病的有前景的治疗方法

On the Right Track to Treat Movement Disorders: Promising Therapeutic Approaches for Parkinson's and Huntington's Disease.

作者信息

Troncoso-Escudero Paulina, Sepulveda Denisse, Pérez-Arancibia Rodrigo, Parra Alejandra V, Arcos Javiera, Grunenwald Felipe, Vidal Rene L

机构信息

Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.

Faculty of Medicine, Biomedical Neuroscience Institute, University of Chile, Santiago, Chile.

出版信息

Front Aging Neurosci. 2020 Sep 3;12:571185. doi: 10.3389/fnagi.2020.571185. eCollection 2020.

Abstract

Movement disorders are neurological conditions in which patients manifest a diverse range of movement impairments. Distinct structures within the basal ganglia of the brain, an area involved in movement regulation, are differentially affected for every disease. Among the most studied movement disorder conditions are Parkinson's (PD) and Huntington's disease (HD), in which the deregulation of the movement circuitry due to the loss of specific neuronal populations in basal ganglia is the underlying cause of motor symptoms. These symptoms are due to the loss principally of dopaminergic neurons of the substantia nigra (SN) par compacta and the GABAergic neurons of the striatum in PD and HD, respectively. Although these diseases were described in the 19th century, no effective treatment can slow down, reverse, or stop disease progression. Available pharmacological therapies have been focused on preventing or alleviating motor symptoms to improve the quality of life of patients, but these drugs are not able to mitigate the progressive neurodegeneration. Currently, considerable therapeutic advances have been achieved seeking a more efficacious and durable therapeutic effect. Here, we will focus on the new advances of several therapeutic approaches for PD and HD, starting with the available pharmacological treatments to alleviate the motor symptoms in both diseases. Then, we describe therapeutic strategies that aim to restore specific neuronal populations or their activity. Among the discussed strategies, the use of Neurotrophic factors (NTFs) and genetic approaches to prevent the neuronal loss in these diseases will be described. We will highlight strategies that have been evaluated in both Parkinson's and Huntington's patients, and also the ones with strong preclinical evidence. These current therapeutic techniques represent the most promising tools for the safe treatment of both diseases, specifically those aimed to avoid neuronal loss during disease progression.

摘要

运动障碍是一类神经疾病,患者会表现出各种各样的运动障碍。大脑基底神经节内不同的结构参与运动调节,每种疾病对这些结构的影响各不相同。帕金森病(PD)和亨廷顿舞蹈病(HD)是研究最多的运动障碍疾病,基底神经节中特定神经元群的丧失导致运动回路失调,是运动症状的根本原因。这些症状分别主要是由于PD中黑质致密部多巴胺能神经元的丧失以及HD中纹状体GABA能神经元的丧失。尽管这些疾病在19世纪就已被描述,但尚无有效的治疗方法能够减缓、逆转或阻止疾病进展。现有的药物治疗主要集中在预防或减轻运动症状以提高患者生活质量,但这些药物无法减轻进行性神经退行性变。目前,在寻求更有效和持久的治疗效果方面已经取得了相当大的治疗进展。在这里,我们将重点介绍PD和HD几种治疗方法的新进展,首先从缓解这两种疾病运动症状的现有药物治疗开始。然后,我们描述旨在恢复特定神经元群或其活性的治疗策略。在讨论的策略中,将描述使用神经营养因子(NTFs)和基因方法来预防这些疾病中的神经元丧失。我们将强调在帕金森病和亨廷顿舞蹈病患者中都已评估过的策略,以及那些有强有力临床前证据的策略。这些当前的治疗技术是安全治疗这两种疾病最有前景的工具,特别是那些旨在避免疾病进展过程中神经元丧失的技术。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8293/7497570/e4fec1d19e6b/fnagi-12-571185-g0001.jpg

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