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靶向星形胶质细胞治疗帕金森病的神经保护策略。

Therapeutic Strategy of Targeting Astrocytes for Neuroprotection in Parkinson's Disease.

机构信息

Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama. Japan.

出版信息

Curr Pharm Des. 2017;23(33):4936-4947. doi: 10.2174/1381612823666170710163731.

Abstract

Parkinson's disease (PD) is one of common neurodegenerative diseases, which shows motor symptoms including tremor, bradykinesia, rigidity and postural instability. It also involves non-motor symptoms such as cognitive impairment, mental manifestation, autonomic disorder and sensory disturbance. Although treatments to improve the motor disability in PD are being assessed at present, the main challenge remains that is the development of neuroprotective or disease-modifying treatments. Therefore, it is desirable to find approaches that can inhibit the progression of dopaminergic neurodegeneration. Astrocytes are known to play an important role in the maintenance of the neuronal environment and exert neuroprotective effects. Additionally, astrocyte dysfunction increases the susceptibility of neurons to cytotoxicity. We have demonstrated neuroprotective approaches in parkinsonian models in various studies targeting astrocytes. In this article, we summarize the neuroprotective function of astrocytes in the brain, involvement of astrocyte dysfunction in neurodegeneration, and experimental approaches to dopaminergic neuroprotection. We review findings reported in several papers including our own studies. We also address target molecules and pivotal pathways in astrocytes for dopaminergic neuroprotection. The review discusses new promising therapeutic strategies to prevent dopaminergic neurodegeneration in PD.

摘要

帕金森病(PD)是一种常见的神经退行性疾病,其运动症状包括震颤、运动迟缓、肌肉僵直和姿势不稳。它还涉及非运动症状,如认知障碍、精神表现、自主神经紊乱和感觉障碍。尽管目前正在评估改善 PD 运动障碍的治疗方法,但主要挑战仍然是开发神经保护或疾病修饰治疗方法。因此,寻找能够抑制多巴胺能神经退行性变的方法是可取的。星形胶质细胞在维持神经元环境和发挥神经保护作用方面起着重要作用。此外,星形胶质细胞功能障碍增加了神经元对细胞毒性的易感性。我们在针对星形胶质细胞的各种帕金森病模型研究中已经证明了神经保护方法。在本文中,我们总结了星形胶质细胞在大脑中的神经保护功能、星形胶质细胞功能障碍在神经退行性变中的作用以及多巴胺能神经保护的实验方法。我们综述了包括我们自己的研究在内的几篇论文的研究结果。我们还讨论了星形胶质细胞中用于多巴胺能神经保护的靶分子和关键途径。该综述讨论了预防 PD 中多巴胺能神经退行性变的新的有前途的治疗策略。

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