Schaeffer Eva, Kluge Annika, Böttner Martina, Zunke Friederike, Cossais Francois, Berg Daniela, Arnold Philipp
Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany.
Front Cell Dev Biol. 2020 Sep 8;8:573696. doi: 10.3389/fcell.2020.573696. eCollection 2020.
Parkinson's disease (PD) is marked by different kinds of pathological features, one hallmark is the aggregation of α-synuclein (aSyn). The development of aSyn pathology in the substantia nigra is associated to the manifestation of motor deficits at the time of diagnosis. However, most of the patients suffer additionally from non-motor symptoms, which may occur already in the prodromal phase of the disease years before PD is diagnosed. Many of these symptoms manifest in the gastrointestinal system (GIT) and some data suggest a potential link to the occurrence of pathological aSyn forms within the GIT. These clinical and pathological findings lead to the idea of a gut-brain route of aSyn pathology in PD. The identification of pathological aSyn in the intestinal system, e.g., by GIT biopsies, is therefore of highest interest for early diagnosis and early intervention in the phase of formation and propagation of aSyn. However, reliable methods to discriminate between physiological and pathological forms of enteral aSyn on the cellular and biochemical level are still missing. Moreover, a better understanding of the physiological function of aSyn within the GIT as well as its structure and pathological aggregation pathways are crucial to understand its role within the enteric nervous system and its spreading from the gut to the brain. In this review, we summarize clinical manifestations of PD in the GIT, and discuss biochemical findings from enteral biopsies. The relevance of pathological aSyn forms, their connection to the gut-brain axis and new developments to identify pathologic forms of aSyn by structural features are critically reviewed.
帕金森病（PD）具有多种病理特征，其中一个标志是α-突触核蛋白（aSyn）的聚集。黑质中aSyn病理变化的发展与诊断时运动功能障碍的表现相关。然而，大多数患者还伴有非运动症状，这些症状可能在疾病的前驱期就已出现，甚至在PD被诊断前数年。其中许多症状表现在胃肠道系统（GIT），一些数据表明其与GIT内病理性aSyn形式的出现存在潜在联系。这些临床和病理发现引发了关于PD中aSyn病理的肠-脑途径的观点。因此，通过GIT活检等方法在肠道系统中鉴定病理性aSyn，对于在aSyn形成和传播阶段进行早期诊断和早期干预具有至关重要的意义。然而，在细胞和生化水平上区分肠道aSyn生理形式和病理形式的可靠方法仍然缺乏。此外，更好地了解aSyn在GIT内的生理功能及其结构和病理聚集途径，对于理解其在肠神经系统中的作用以及从肠道向大脑的传播至关重要。在本综述中，我们总结了PD在GIT中的临床表现，并讨论了肠道活检的生化结果。对病理性aSyn形式的相关性、它们与肠-脑轴的联系以及通过结构特征识别aSyn病理形式的新进展进行了批判性综述。
