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破解帕金森病之谜:从药物、手术到干细胞与基因——当前及未来治疗策略的全面综述

Unravelling the Parkinson's puzzle, from medications and surgery to stem cells and genes: a comprehensive review of current and future management strategies.

作者信息

Chandrababu Krishnapriya, Radhakrishnan Vineeth, Anjana A S, Rajan Rahul, Sivan Unnikrishnan, Krishnan Syam, Baby Chakrapani P S

机构信息

Centre for Neuroscience, Department of Biotechnology, Cochin University for Science and Technology, Kochi, Kerala, 682 022, India.

Comprehensive Care Centre for Movement Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.

出版信息

Exp Brain Res. 2024 Jan;242(1):1-23. doi: 10.1007/s00221-023-06735-1. Epub 2023 Nov 28.

DOI:10.1007/s00221-023-06735-1
PMID:38015243
Abstract

Parkinson's disease (PD) is a neurodegenerative disorder, prevalent in the elderly population. Neuropathological hallmarks of PD include loss of dopaminergic cells in the nigro-striatal pathway and deposition of alpha-synuclein protein in the neurons and synaptic terminals, which lead to a complex presentation of motor and non-motor symptoms. This review focuses on various aspects of PD, from clinical diagnosis to currently accepted treatment options, such as pharmacological management through dopamine replacement and surgical techniques such as deep brain stimulation (DBS). The review discusses in detail the potential of emerging stem cell-based therapies and gene therapies to be adopted as a cure, in contrast to the present symptomatic treatment in PD. The potential sources of stem cells for autologous and allogeneic stem cell therapy have been discussed, along with the progress evaluation of pre-clinical and clinical trials. Even though recent techniques hold great potential to improve the lives of PD patients, we present the importance of addressing the safety, efficacy, ethical, cost, and regulatory concerns before scaling them to clinical use.

摘要

帕金森病(PD)是一种神经退行性疾病,在老年人群中普遍存在。PD的神经病理学特征包括黑质-纹状体通路中多巴胺能细胞的丧失以及α-突触核蛋白在神经元和突触终末的沉积,这导致了运动和非运动症状的复杂表现。本综述聚焦于PD的各个方面,从临床诊断到目前公认的治疗选择,如通过多巴胺替代进行药物治疗以及深部脑刺激(DBS)等手术技术。与目前PD的对症治疗相比,本综述详细讨论了新兴的基于干细胞疗法和基因疗法作为治愈方法的潜力。已经讨论了用于自体和异体干细胞治疗的干细胞潜在来源,以及临床前和临床试验的进展评估。尽管最近的技术在改善PD患者生活方面具有巨大潜力,但我们强调在将这些技术扩大到临床应用之前,解决安全性、有效性、伦理、成本和监管问题的重要性。

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Unravelling the Parkinson's puzzle, from medications and surgery to stem cells and genes: a comprehensive review of current and future management strategies.破解帕金森病之谜:从药物、手术到干细胞与基因——当前及未来治疗策略的全面综述
Exp Brain Res. 2024 Jan;242(1):1-23. doi: 10.1007/s00221-023-06735-1. Epub 2023 Nov 28.
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本文引用的文献

1
Probing Gut Participation in Parkinson's Disease Pathology and Treatment via Stem Cell Therapy.通过干细胞疗法探究肠道参与帕金森病病理和治疗的作用。
Int J Mol Sci. 2023 Jun 25;24(13):10600. doi: 10.3390/ijms241310600.
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Curcumin alleviates 1-methyl- 4-phenyl- 1,2,3,6-tetrahydropyridine- induced Parkinson's disease in mice via modulating gut microbiota and short-chain fatty acids.姜黄素通过调节肠道微生物群和短链脂肪酸减轻1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的小鼠帕金森病。
Front Pharmacol. 2023 Jun 14;14:1198335. doi: 10.3389/fphar.2023.1198335. eCollection 2023.
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Parkinson's disease: Are gut microbes involved?
普拉克索使外部苍白球过度活跃,并损害帕金森病小鼠模型的决策能力。
Int J Mol Sci. 2024 Aug 14;25(16):8849. doi: 10.3390/ijms25168849.
帕金森病:肠道微生物是否与之有关?
Brain Behav. 2023 Aug;13(8):e3130. doi: 10.1002/brb3.3130. Epub 2023 Jun 20.
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Mesenchymal stem-cell-derived microvesicles ameliorate MPTP-induced neurotoxicity in mice: a role of the gut-microbiota-brain axis.间充质干细胞来源的微囊泡减轻 MPTP 诱导的小鼠神经毒性:肠道微生物群-脑轴的作用。
Psychopharmacology (Berl). 2023 May;240(5):1103-1118. doi: 10.1007/s00213-023-06348-0. Epub 2023 Mar 7.
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Cell therapy for Parkinson's disease with induced pluripotent stem cells.诱导多能干细胞用于帕金森病的细胞治疗
Inflamm Regen. 2023 Feb 27;43(1):16. doi: 10.1186/s41232-023-00269-3.
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Deciphering the gut microbiome in neurodegenerative diseases and metagenomic approaches for characterization of gut microbes.解析神经退行性疾病中的肠道微生物组和用于肠道微生物特征分析的宏基因组方法。
Biomed Pharmacother. 2022 Dec;156:113958. doi: 10.1016/j.biopha.2022.113958. Epub 2022 Nov 7.
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Recent developments in nucleic acid-based therapies for Parkinson's disease: Current status, clinical potential, and future strategies.帕金森病基于核酸疗法的最新进展:现状、临床潜力及未来策略
Front Pharmacol. 2022 Oct 20;13:986668. doi: 10.3389/fphar.2022.986668. eCollection 2022.
8
Immunogenicity and toxicity of AAV gene therapy.AAV 基因治疗的免疫原性和毒性。
Front Immunol. 2022 Aug 12;13:975803. doi: 10.3389/fimmu.2022.975803. eCollection 2022.
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Front Cell Dev Biol. 2022 Jul 4;9:760618. doi: 10.3389/fcell.2021.760618. eCollection 2021.
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Glucocerebrosidase Mutations Cause Mitochondrial and Lysosomal Dysfunction in Parkinson's Disease: Pathogenesis and Therapeutic Implications.葡糖脑苷脂酶突变导致帕金森病中的线粒体和溶酶体功能障碍:发病机制及治疗意义
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