Temporal and Spatial Dynamics of Enteric Glial Cell Involvement in Parkinson’s Disease: A Literature Review

Abstract

Introduction: Enteric glial cells (EGCs) are critical regulators of gastrointestinal (GI) homeostasis and are implicated in early Parkinson’s disease (PD) pathogenesis. Disruption of EGCs can trigger gut inflammation and propagation of pathological α-synuclein (α-syn) to the central nervous system (CNS). Investigating both the temporal dynamics of EGC activity across stages and spatial differences among gut regions is essential to identify when and where their shift from protective to pathological roles occurs. This review addresses these dynamics to understand PD progression better and propose EGC-targeted strategies.

Methods: A systematic search in May 2025 of PubMed and Google Scholar (Jan 2012–Apr 2025) yielded 842 articles. Prioritizing primary research on enteric glial cells in Parkinson’s disease and excluding reviews or unrelated studies, 26 articles ultimately met the inclusion criteria for this review.

Results: Regarding temporal dynamics, animal models demonstrate that EGC activation and inflammation emerge in the prodromal phase, preceding motor deficits. Subacute toxin models exhibit variable glial stress responses, whereas chronic and protopathic models illustrate neurochemical remodeling and the potential spread of pathology from the ENS to the CNS. Spatially, animal studies indicate region-specific vulnerability: the gastric myenteric plexus exhibits early α-syn accumulation; the distal ileum and proximal colon display oxidative stress and neurotransmitter imbalances; and the sigmoid colon shows TRL4-mediated inflammation. In parallel, human clinical findings corroborate distinct regional alterations, particularly in the duodenum, characterized by reactive gliosis and α-syn aggregates, and the ascending colon, where elevated pro-inflammatory cytokines correlated with increased expression of reactive glial marker GFAP and the developmental marker Sox-10.

Discussion: The results support the hypothesis of PD pathology originating in the gut, with EGCs playing a critical role. Understanding these dynamics could help develop region-specific, EGC-based biomarkers for early diagnosis in the prodromal phase and guide targeted interventions. Future research should incorporate longitudinal tracking of EGC activity, single-cell multi-omics, and targeted interventions in PD models to establish causality.

Conclusion: EGCs respond to early gut dysfunction and influence subsequent PD progression. Their time and region-specific activation may explain not only GI symptoms but also PD pathology, suggesting possible biomarkers or treatment targets.