PARKINSON’S disease (PD), a progressive neurodegenerative disorder impacting over 10 million people worldwide, is defined by the aggregation of misfolded α-synuclein (aSyn) in the substantia nigra pars compacta, leading to the hallmark motor symptoms of tremor, rigidity, and bradykinesia. However, beyond the central nervous system, emerging research underscores the significance of gastrointestinal (GI) involvement in PD, suggesting the gut-brain axis may play a pivotal role in disease progression.
A recent review delves into the involvement of gut neuropeptides, key modulators of gut-brain communication, in PD pathophysiology. Misfolded aSyn aggregates have been identified in the GI tract, and non-motor GI symptoms can precede motor manifestations by up to 20 years. This timeline highlights the importance of the bidirectional communication between the enteric nervous system and the central nervous system. Despite growing evidence linking microbiome alterations and intestinal inflammation to PD, the functional role of gut neuropeptide signaling in these processes remains largely uncharted.
Neuropeptides such as vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), ghrelin, cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and substance P (SP) are critical regulators of gut-brain communication and immune responses. In animal models of PD, dysregulation of these neuropeptides has been associated with pathological changes, suggesting that they may influence both gut barrier integrity and neuroimmune signaling pathways.
This review consolidates current findings on how microbial metabolites and immune factors may influence gut neuropeptide activity, potentially driving aSyn aggregation within the enteric nervous system and altering downstream neuroimmune responses. Despite these compelling connections, gut neuropeptides remain an underexplored avenue in PD research. Understanding their role could illuminate new therapeutic targets within the gut-brain axis, offering a more comprehensive approach to managing Parkinson’s disease.
Reference:
Patterson A et al. Gut neuropeptide involvement in Parkinson’s disease. Int Rev Neurobiol. 2024;174:33-64.
