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.
Highlights
Parkinson’s disease (PD) is the second most frequent neurological disease afterAlzheimer’s disease, and affects 1% of the population above 60 years of age worldwide [1].Clinical hallmarks of the disease include resting tremor, rigidity, bradykinesia, and postural instability, which is primarily attributed to the progressive degeneration of dopaminecontaining neurons in the substantia nigra pars compacta (SNpc) [2,3,4]
Lewy bodies (LB) are found in other regions of the central nervous system (CNS), such as the peripheral and enteric nervous system (ENS) [5,6], and may play a role in the onset of non-motor symptoms associated with the disease
This review describes the most common GI symptoms that affect individuals suffering from PD, and the impact they have on quality of life and disease management
Summary
Alzheimer’s disease, and affects 1% of the population above 60 years of age worldwide [1]. It is clear that some forms of GI dysfunction precede the onset of motor deficits by decades [8] and greatly impact on patient quality of life. Weight loss has been found to precede PD diagnosis by years, and is associated with disease severity as well as duration [9], whilst low body mass index has a significant impact on the life prognosis of PD patients, males [10]. The presence of LBs in the ENS has led to the suggestion that enteric neuronal loss and/or dysfunction may contribute to the development of GI symptoms. Given the limitations of current treatments, we propose a novel approach to the alleviation of GI symptoms by highlighting the intestinal barrier, ENS, and gut microbiome as potential therapeutic avenues, and expand on current emerging therapies and propose several therapeutics that may prove effective through drug repurposing
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