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帕金森病多巴胺能细胞替代和再生策略的研究进展。

Progress in Dopaminergic Cell Replacement and Regenerative Strategies for Parkinson's Disease.

机构信息

Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine , Sun Yat-sen University , No. 74 Zhongshan Road 2 , Guangzhou 510080 , China.

出版信息

ACS Chem Neurosci. 2019 Feb 20;10(2):839-851. doi: 10.1021/acschemneuro.8b00389. Epub 2018 Oct 24.


DOI:10.1021/acschemneuro.8b00389
PMID:30346716
Abstract

Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder symptomatically characterized by resting tremor, rigidity, bradykinesia, and gait impairment. These motor deficits suffered by PD patients primarily result from selective dysfunction or loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc). Most of the existing therapies for PD are based on the replacement of dopamine, which is symptomatically effective in the early stage but becomes increasingly less effective and is accompanied by serious side effects in the advanced stages of the disease. Currently, there are no strategies to slow neuronal degeneration or prevent the progression of PD. Thus, the prospect of regenerating functional dopaminergic neurons is very attractive. Over the last few decades, significant progress has been made in the development of dopaminergic regenerative strategies for curing PD. The most promising approach seems to be cell-replacement therapy (CRT) using human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), which are unlimitedly available and have gained much success in preclinical trials. Despite the challenges, stem cell-based CRT will make significant steps toward the clinic in the coming decade. Alternatively, direct lineage reprogramming, especially in situ direct conversion of glia cells to induced neurons, which exhibits some advantages including no ethical concerns, no risk of tumor formation, and even no need for transplantation, has gained much attention recently. Evoking the endogenous regeneration ability of neural stem cells (NSCs) is an idyllic method of dopaminergic neuroregeneration which remains highly controversial. Here, we review many of these advances, highlighting areas and strategies that might be particularly suited to the development of regenerative approaches that restore dopaminergic function in PD.

摘要

帕金森病(PD)是一种慢性进行性神经退行性疾病,其症状特征为静止性震颤、僵硬、运动迟缓以及步态障碍。PD 患者的这些运动缺陷主要是由于黑质致密部(SNpc)中多巴胺能神经元的选择性功能障碍或丧失所致。目前 PD 的大多数治疗方法都是基于多巴胺的替代疗法,这种疗法在疾病早期具有明显的疗效,但在疾病晚期效果越来越差,并伴有严重的副作用。目前,还没有减缓神经元退化或阻止 PD 进展的策略。因此,再生功能性多巴胺能神经元的前景非常有吸引力。在过去的几十年中,在开发用于治疗 PD 的多巴胺能再生策略方面取得了重大进展。最有前途的方法似乎是使用人胚胎干细胞(ESCs)或诱导多能干细胞(iPSCs)的细胞替代疗法(CRT),这些细胞是无限可用的,并且在临床前试验中取得了很大的成功。尽管存在挑战,但基于干细胞的 CRT 将在未来十年内朝着临床应用迈出重要的一步。或者,直接谱系重编程,特别是在原位将神经胶质细胞直接转化为诱导神经元,具有一些优势,包括没有伦理问题、没有肿瘤形成的风险,甚至不需要移植,最近引起了广泛关注。激发神经干细胞(NSCs)的内源性再生能力是多巴胺能神经再生的理想方法,但仍存在很大争议。在这里,我们回顾了其中的许多进展,强调了可能特别适合开发恢复 PD 中多巴胺能功能的再生方法的领域和策略。

相似文献

[1]
Progress in Dopaminergic Cell Replacement and Regenerative Strategies for Parkinson's Disease.

ACS Chem Neurosci. 2018-10-24

[2]
Cell therapy for Parkinson's disease: Functional role of the host immune response on survival and differentiation of dopaminergic neuroblasts.

Brain Res. 2016-5-1

[3]
Implications of Parkinson's disease pathophysiology for the development of cell replacement strategies and drug discovery in neurodegenerative diseases.

CNS Neurol Disord Drug Targets. 2012-11-1

[4]
Potential application of induced pluripotent stem cells in cell replacement therapy for Parkinson's disease.

CNS Neurol Disord Drug Targets. 2011-6

[5]
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Transl Neurodegener. 2020-1-7

[6]
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Expert Rev Neurother. 2011-6

[7]
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Neuroscience. 2021-5-21

[8]
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Curr Stem Cell Res Ther. 2024

[9]
Research progress of neural stem cells as a source of dopaminergic neurons for cell therapy in Parkinson's disease.

Mol Biol Rep. 2024-2-24

[10]
Treatment of Parkinson's disease using cell transplantation.

Philos Trans R Soc Lond B Biol Sci. 2015-10-19

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[4]
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[5]
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[6]
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[7]
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