运动训练对帕金森病黑质纹状体神经保护作用的系统评价
Effects of exercise training on nigrostriatal neuroprotection in Parkinson's disease: a systematic review.
作者信息
Ishaq Shahid, Shah Iqbal Ali, Lee Shin-Da, Wu Bor-Tsang
机构信息
PhD Program in Healthcare Science, College of Healthcare Science, China Medical University, Taichung, Taiwan.
Department of Physical Therapy, China Medical University, Taichung, Taiwan.
出版信息
Front Neurosci. 2025 Jan 8;18:1464168. doi: 10.3389/fnins.2024.1464168. eCollection 2024.
INTRODUCTION
Parkinson's disease (PD) is characterized by progressive neurodegeneration within the nigrostriatum, leading to motor dysfunction. This systematic review aimed to summarize the effects of various exercise training regimens on protein or gene expression within the nigrostriatum and their role in neuroprotection and motor function improvement in animal models of Parkinson's disease (PD).
METHODS
PubMed, EMBASE, and Web of Science were searched up to June 2024 and included sixteen studies that adhere to PRISMA guidelines and CAMARADES checklist scores ranging from 4 to 6 out of 10. Various exercise training regimens, administered 5 days per week for 6.5 weeks, were applied to MPTP, 6-OHDA, and PFF-α-synuclein-induced PD animal models.
RESULTS
Exercise training was found to downregulate the inflammatory pathway by attenuating α-synuclein aggregation, inhibiting the TLR/MyD88/IκBα signaling cascade and NF-κB phosphorylation, and decreasing pro-inflammatory cytokines IL-1β and TNF-α while increasing anti-inflammatory cytokines IL-10 and TGF-β within the nigrostriatum. It also inhibited the ASC and NLRP3 inflammasome complex and reduced the BAX/ Bcl-2 ratio and caspase-1/3 proteins, thereby decreasing neuronal apoptosis in the nigrostriatum. Exercise training elevated the expression of Pro-BDNF, BDNF, GDNF, TrkB, and Erk1/2, providing neurotrophic support to dopaminergic neurons. Furthermore, it upregulated the dopaminergic signaling pathway by increasing the expression of TH, DAT, PSD-95, and synaptophysin in the nigrostriatum.
DISCUSSION
The findings suggested that exercise training downregulated inflammatory and apoptotic pathways while upregulated BDNF/GDNF pathways and dopaminergic signaling within the nigrostriatum. These molecular changes contributed to neuroprotection, reduced dopaminergic neuron loss, and improved motor function in PD animal models.
SYSTEMATIC REVIEW REGISTRATION
CRD42024484537 https://www.crd.york.ac.uk/prospero/#recordDetails.
引言
帕金森病（PD）的特征是黑质纹状体内进行性神经退行性变，导致运动功能障碍。本系统评价旨在总结各种运动训练方案对帕金森病（PD）动物模型黑质纹状体内蛋白质或基因表达的影响及其在神经保护和运动功能改善中的作用。
方法
检索截至2024年6月的PubMed、EMBASE和Web of Science，纳入16项符合PRISMA指南且CAMARADES清单评分在4至6分（满分10分）之间的研究。将每周5天、共6.5周的各种运动训练方案应用于MPTP、6-OHDA和PFF-α-突触核蛋白诱导的PD动物模型。
结果
发现运动训练通过减弱α-突触核蛋白聚集、抑制TLR/MyD88/IκBα信号级联和NF-κB磷酸化、降低促炎细胞因子IL-1β和TNF-α，同时增加黑质纹状体内抗炎细胞因子IL-10和TGF-β来下调炎症途径。它还抑制了ASC和NLRP3炎性小体复合物，降低了BAX/Bcl-2比值和caspase-1/3蛋白，从而减少黑质纹状体内的神经元凋亡。运动训练提高了Pro-BDNF、BDNF、GDNF、TrkB和Erk1/2的表达，为多巴胺能神经元提供神经营养支持。此外，它通过增加黑质纹状体内TH、DAT、PSD-95和突触素的表达来上调多巴胺能信号通路。
讨论
研究结果表明，运动训练下调了黑质纹状体内的炎症和凋亡途径，同时上调了BDNF/GDNF途径和多巴胺能信号。这些分子变化有助于在PD动物模型中发挥神经保护作用、减少多巴胺能神经元损失并改善运动功能。
系统评价注册
CRD42024484537 https://www.crd.york.ac.uk/prospero/#recordDetails 。
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