摘要
帕金森病(PD)是一种以运动和非运动障碍为主要特征的疾病,主要原因是黑质多巴胺能细胞的丢失和黑质纹状体通路的破坏。尽管在治疗帕金森病的前沿方法上取得了令人尊敬的进展,但仍存在许多挑战,使这种疾病无法得到明确的治疗。本文综述了各种非药物治疗方法的发展,重点介绍了PD的前沿治疗方法,包括基于基因和干细胞的治疗、神经营养因子的靶向传递以及经颅磁刺激(TMS)、经颅直流刺激(TDCS)和深部脑刺激(DBS)等脑刺激技术。综述了多种基因治疗策略,包括腺苷相关病毒-谷氨酸脱羧酶(AAV-GAD)、AAV-芳香L-氨基酸脱羧酶(AAV-AADC)、Lenti-AADC/酪氨酸羟化酶/鸟苷三磷酸环水解酶I(Lenti-AADC/TH/GTP-CH1)、AAV-Neurturin(AAV-NRTN)、α-合成核苷沉默和PRKN基因传递。并对这些方法的优缺点和试验结果进行了讨论。最后,描述了PD治疗失败的原因,希望与炒作分离。
关键词: PRKN基因传递,α-合成核蛋白沉默,tDCS,DBS,细胞治疗,AAV-GAD.
Current Gene Therapy
Title:Cellular, Molecular and Non-Pharmacological Therapeutic Advances for the Treatment of Parkinson's Disease: Separating Hope from Hype
Volume: 18 Issue: 4
关键词: PRKN基因传递,α-合成核蛋白沉默,tDCS,DBS,细胞治疗,AAV-GAD.
摘要: Parkinson’s Disease (PD) is a frustrating condition characterized by motor and nonmotor deficits majorly caused by the loss of dopaminergic cells in the Substantia Nigra pars compacta (SNc) and destruction of the nigrostriatal pathway. Despite the very respectable advances in cutting-edge approaches for the treatment of PD, there exist numerous challenges that have incapacitated the definitive treatment of this disease. This review emphasized the development of various non-pharmaceutical therapeutic approaches and mainly highlighted the cutting-edge treatments for PD including gene- and stem cell-based therapies, targeted delivery of neurotrophic factors, and brain stimulation techniques such as Transcranial Magnetic Stimulation (TMS), transcranial Direct Current Stimulation (tDCS), and Deep Brain Stimulation (DBS). The review covered various gene therapy strategies including Adeno-Associated Virus-Glutamic Acid Decarboxylase (AAV-GAD), AAV–Aromatic L-Amino Acid Decarboxylase (AAV-AADC), Lenti-AADC/Tyrosine Hydroxylase/Guanosine Triphosphate- Cyclohydrolase I (Lenti-AADC/TH/GTP-CH1), AAV–Neurturin (AAV-NRTN), α-Synuclein silencing, and PRKN gene delivery. Also, the advantages, disadvantages, and the results of trials of these methods were discussed. Finally, reasons for the failure of PD treatment were described, with the hopes separated from hypes.
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Cellular, Molecular and Non-Pharmacological Therapeutic Advances for the Treatment of Parkinson's Disease: Separating Hope from Hype, Current Gene Therapy 2018; 18 (4) . https://dx.doi.org/10.2174/1566523218666180910163401
DOI https://dx.doi.org/10.2174/1566523218666180910163401 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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