Rietdijk Carmen D, Perez-Pardo Paula, Garssen Johan, van Wezel Richard J A, Kraneveld Aletta D
Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht , Netherlands.
Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands; Nutricia Research, Utrecht, Netherlands.
Front Neurol. 2017 Feb 13;8:37. doi: 10.3389/fneur.2017.00037. eCollection 2017.
Parkinson's disease (PD) is a neurodegenerative disorder for which there is no cure. Most patients suffer from sporadic PD, which is likely caused by a combination of genetic and environmental factors. Braak's hypothesis states that sporadic PD is caused by a pathogen that enters the body the nasal cavity, and subsequently is swallowed and reaches the gut, initiating Lewy pathology (LP) in the nose and the digestive tract. A staging system describing the spread of LP from the peripheral to the central nervous system was also postulated by the same research group. There has been criticism to Braak's hypothesis, in part because not all patients follow the proposed staging system. Here, we review literature that either supports or criticizes Braak's hypothesis, focused on the enteric route, digestive problems in patients, the spread of LP on a tissue and a cellular level, and the toxicity of the protein αSynuclein (αSyn), which is the major constituent of LP. We conclude that Braak's hypothesis is supported by , and clinical evidence. However, we also conclude that the staging system of Braak only describes a specific subset of patients with young onset and long duration of the disease.
帕金森病（PD）是一种无法治愈的神经退行性疾病。大多数患者患有散发性帕金森病，这可能是由遗传和环境因素共同导致的。布拉克假说认为，散发性帕金森病是由一种病原体引起的，该病原体通过鼻腔进入人体，随后被吞咽并到达肠道，从而在鼻腔和消化道引发路易体病理改变（LP）。同一研究团队还提出了一个描述LP从外周神经系统向中枢神经系统扩散的分期系统。对布拉克假说存在一些批评，部分原因是并非所有患者都遵循所提出的分期系统。在此，我们回顾了支持或批评布拉克假说的文献，重点关注肠道途径、患者的消化问题、LP在组织和细胞水平上的扩散，以及蛋白质α-突触核蛋白（αSyn）的毒性，αSyn是LP的主要成分。我们得出结论，布拉克假说得到了 和临床证据的支持。然而，我们也得出结论，布拉克的分期系统仅描述了疾病发病年龄较轻且病程较长的特定患者亚群。
