Gut-brain axis and the spread of α-synuclein pathology: Vagal highway or dead end?
Gut-brain axis and the spread of α-synuclein pathology: Vagal highway or dead end?
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DOI：
10.1002/mds.27556
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发表时间：
2019-03-01
影响因子：
8.6
通讯作者：
Lang, Anthony E.
中科院分区：
文献类型：
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作者：
Breen, David P.;Halliday, Glenda M.;Lang, Anthony E.
从外周神经系统到中枢神经系统的α-突触核蛋白病理学扩散可能是帕金森病的一个重要病因，尽管关于其与神经元损失的相关性存在一些未回答的问题。实验证据已经突出了胃肠道作为聚集的α-突触核蛋白的潜在起始点，其中迷走神经充当病理可通过其传递到下脑干的“高速公路”。这篇综述首先强调了关键的研究表明，α-突触核蛋白病理有能力从胃肠道的某些部位传播到大脑（反之亦然）。我们继续评估最近的流行病学研究，这些研究表明迷走神经切断术和阑尾切除术可能具有降低帕金森病风险的潜力。最后，我们讨论了胃肠道中可能首先引发α-突触核蛋白聚集的因素（如肠道微生物群的生态失调，感染和炎症），以及大脑中α-突触核蛋白病理分布的其他潜在机制。(c)2019国际帕金森和运动障碍协会
Spread of alpha-synuclein pathology from the peripheral to central nervous system may be an important etiological factor in Parkinson's disease, although there are some unanswered questions about its correlation with neuronal loss. Experimental evidence has highlighted the gastrointestinal tract as a potential starting point for aggregated alpha-synuclein, with the vagus nerve acting as a "highway" by which pathology may be transmitted to the lower brain stem. This review begins by highlighting the key studies demonstrating that alpha-synuclein pathology has the ability to spread from certain sites in the gastrointestinal tract to the brain (and vice versa). We go on to assess the recent epidemiological studies that have shown that vagotomy and appendectomy may have the potential to reduce the risk of developing Parkinson's disease. Finally, we discuss the factors in the gastrointestinal tract (such as dysbiosis of the gut microbiota, infection, and inflammation) that may trigger alpha-synuclein aggregation in the first place, as well as other potential mechanisms underlying the distribution of alpha-synuclein pathology in the brain. (c) 2019 International Parkinson and Movement Disorder Society