Han Myat Noe, Finkelstein David I, McQuade Rachel M, Diwakarla Shanti
Gut-Axis Injury and Repair Laboratory, Department of Medicine Western Health, University of Melbourne, Melbourne, VIC 3021, Australia.
The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3010, Australia.
J Pers Med. 2022 Jan 21;12(2):144. doi: 10.3390/jpm12020144.
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.
帕金森病（PD）患者胃肠道（GI）异常早在200多年前就有报道；然而，GI功能障碍在PD疾病进展中的程度和作用仍不清楚。GI功能障碍，包括吞咽困难、胃轻瘫和便秘，是PD中最常见的非运动症状。这些症状不仅影响患者生活质量，还使疾病管理复杂化。GI功能障碍（如便秘）的传统治疗途径，如增加纤维和液体摄入量以及使用非处方泻药，对PD患者通常无效，而鸟苷酸环化酶C激动剂和选择性5-羟色胺4受体激动剂等已获批的化合物疗效有限。因此，确定缓解PD引起的GI功能障碍的新疗法潜在靶点对于改善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，PD病理学及其在CNS损伤中涉及的机制相对已得到充分表征，PD在肠神经系统（ENS）细胞和组织水平的作用仍不清楚，这使得缓解或逆转GI症状变得困难。然而，对了解GI tract如何参与各种疾病状态（如PD）的兴趣再度兴起，已促成了新治疗途径的发现。本综述重点关注常见的与PD相关的GI症状，并总结了现有的治疗方法及其局限性。我们提出，通过靶向肠道屏障、ENS和/或肠道微生物群，可能成功缓解与PD相关的GI症状，并讨论了新兴疗法以及可重新用于靶向这些领域的潜在药物。
