Killinger Bryan Andrew, Labrie Viviane
Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI USA.
Centre for Addiction and Mental Health, Toronto, ON Canada.
NPJ Parkinsons Dis. 2017 Nov 24;3:33. doi: 10.1038/s41531-017-0035-z. eCollection 2017.
The aberrant aggregation of the protein α-synuclein is thought to be involved in Parkinson's disease (PD). However, the factors that lead to initiation and propagation of α-synuclein aggregation are not clearly understood. Recently, the hypothesis that α-synuclein aggregation spreads via a prion-like mechanism originating in the gut has gained much scientific attention. If α-synuclein spreads via a prion-like mechanism, then an important question becomes, what are the origins of this prion-like species? Here we review the possibility that α-synuclein aggregation could be seeded via the ingestion of a prion-like α-synuclein species contained within food products originating from vertebrates. To do this, we highlight current evidence for the gut-to-brain hypothesis of PD, and put this in context of available routes of α-synuclein prion infectivity via the gastrointestinal (GI) tract. We then discuss meat as a ready exogenous source of α-synuclein and how certain risk factors, including inflammation, may allow for dietary α-synuclein to pass from the GI lumen into the host to induce pathology. Lastly, we review epidemiological evidence that dietary factors may be involved in PD. Overall, research to date has yet to directly test the contribution of dietary α-synuclein to the mechanism of initiation and progression of the disease. However, numerous experimental findings, including the potent seeding and spreading behavior of α-synuclein fibrils, seem to support, at least in part, the feasibility of an infection with a prion α-synuclein particle via the GI tract. Further studies are required to determine whether dietary α-synuclein contributes to seeding pathology in the gut.
蛋白质α-突触核蛋白的异常聚集被认为与帕金森病（PD）有关。然而，导致α-突触核蛋白聚集起始和传播的因素尚不清楚。最近，α-突触核蛋白聚集通过源自肠道的朊病毒样机制传播的假说引起了广泛的科学关注。如果α-突触核蛋白通过朊病毒样机制传播，那么一个重要的问题就变成了，这种朊病毒样物种的起源是什么？在这里，我们回顾了α-突触核蛋白聚集可能通过摄入源自脊椎动物的食品中所含的朊病毒样α-突触核蛋白物种而引发的可能性。为此，我们强调了目前关于PD的肠道到大脑假说的证据，并将其置于α-突触核蛋白朊病毒通过胃肠道（GI）感染的现有途径的背景下。然后，我们讨论肉类作为α-突触核蛋白现成的外源性来源，以及某些风险因素，包括炎症，如何使膳食中的α-突触核蛋白从胃肠道腔进入宿主以诱发病理变化。最后，我们回顾了饮食因素可能与PD有关的流行病学证据。总体而言，迄今为止的研究尚未直接测试膳食α-突触核蛋白对疾病起始和进展机制的贡献。然而，许多实验结果，包括α-突触核蛋白纤维的有效播种和传播行为，似乎至少部分支持了通过胃肠道感染朊病毒α-突触核蛋白颗粒的可行性。需要进一步的研究来确定膳食α-突触核蛋白是否有助于在肠道中引发病理变化。
