Abstract：
Abnormalities in the gastrointestinal (GI) tract of Parkinson\'s disease (PD) sufferers were first reported over 200 years ago; however, the extent and role of GI dysfunction in PD disease progression is still unknown. GI dysfunctions, including dysphagia, gastroparesis, and constipation, are amongst the most prevalent non-motor symptoms in PD. These symptoms not only impact patient quality of life, but also complicate disease management. Conventional treatment pathways for GI dysfunctions (i.e., constipation), such as increasing fibre and fluid intake, and the use of over-the-counter laxatives, are generally ineffective in PD patients, and approved compounds such as guanylate cyclase C agonists and selective 5-hyroxytryptamine 4 receptor agonists have demonstrated limited efficacy. Thus, identification of potential targets for novel therapies to alleviate PD-induced GI dysfunctions are essential to improve clinical outcomes and quality of life in people with PD. Unlike the central nervous system (CNS), where PD pathology and the mechanisms involved in CNS damage are relatively well characterised, the effect of PD at the cellular and tissue level in the enteric nervous system (ENS) remains unclear, making it difficult to alleviate or reverse GI symptoms. However, the resurgence of interest in understanding how the GI tract is involved in various disease states, such as PD, has resulted in the identification of novel therapeutic avenues. This review focuses on common PD-related GI symptoms, and summarizes the current treatments available and their limitations. We propose that by targeting the intestinal barrier, ENS, and/or the gut microbiome, may prove successful in alleviating PD-related GI symptoms, and discuss emerging therapies and potential drugs that could be repurposed to target these areas.
摘要：
200多年前首次报道了帕金森病（PD）患者的胃肠道（GI）异常；然而，胃肠道功能障碍在PD疾病进展中的程度和作用尚不清楚.胃肠道功能障碍,包括吞咽困难,胃轻瘫,便秘，是PD中最常见的非运动症状之一。这些症状不仅影响患者的生活质量,但也使疾病管理复杂化。胃肠道功能障碍的常规治疗途径(即，便秘)，例如增加纤维和液体的摄入量，以及使用非处方泻药，在PD患者中通常无效，和批准的化合物如鸟苷酸环化酶C激动剂和选择性5-羟色胺4受体激动剂已经证明了有限的功效。因此，确定缓解PD诱导的胃肠道功能障碍的新疗法的潜在靶标对于改善PD患者的临床结局和生活质量至关重要.与中枢神经系统（CNS）不同，其中PD病理学和中枢神经系统损伤的机制相对较好地表征，PD在肠神经系统（ENS）的细胞和组织水平的作用尚不清楚，很难缓解或逆转胃肠道症状。然而,对了解胃肠道如何参与各种疾病状态的兴趣重新兴起，比如PD,已经确定了新的治疗途径。这篇综述的重点是常见的PD相关的胃肠道症状，并总结了目前可用的治疗方法及其局限性。我们建议通过靶向肠屏障，ENS,和/或肠道微生物组，可以成功缓解PD相关的胃肠道症状，并讨论新的疗法和潜在的药物，可以重新利用，以这些领域为目标。
