From the Gut to the Brain: The Role of Enteric Glial Cells and Their Involvement in the Pathogenesis of Parkinson's Disease

Author: Alba Montalbán-Rodríguez1,2, Raquel Abalo1,2,3,4,5, Laura López-Gómez1,2
1 Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcon, Spain.
2 High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain.
3 Associated R+D+i Unit to the Institute of Medicinal Chemistry (IQM), Scientific Research Superior Council (CSIC), 28006 Madrid, Spain.
4 Working Group of Basic Sciences on Pain and Analgesia, Spanish Pain Society, 28046 Madrid, Spain.
5 Working Group of Basic Sciences on Cannabinoids, Spanish Pain Society, 28046 Madrid, Spain.
Conference/Journal: Int J Mol Sci
Date published: 2024 Jan 20
Other: Volume ID: 25 , Issue ID: 2 , Pages: 1294 , Special Notes: doi: 10.3390/ijms25021294. , Word Count: 262

The brain-gut axis has been identified as an important contributor to the physiopathology of Parkinson's disease. In this pathology, inflammation is thought to be driven by the damage caused by aggregation of α-synuclein in the brain. Interestingly, the Braak's theory proposes that α-synuclein misfolding may originate in the gut and spread in a "prion-like" manner through the vagus nerve into the central nervous system. In the enteric nervous system, enteric glial cells are the most abundant cellular component. Several studies have evaluated their role in Parkinson's disease. Using samples obtained from patients, cell cultures, or animal models, the studies with specific antibodies to label enteric glial cells (GFAP, Sox-10, and S100β) seem to indicate that activation and reactive gliosis are associated to the neurodegeneration produced by Parkinson's disease in the enteric nervous system. Of interest, Toll-like receptors, which are expressed on enteric glial cells, participate in the triggering of immune/inflammatory responses, in the maintenance of intestinal barrier integrity and in the configuration of gut microbiota; thus, these receptors might contribute to Parkinson's disease. External factors like stress also seem to be relevant in its pathogenesis. Some authors have studied ways to reverse changes in EGCs with interventions such as administration of Tryptophan-2,3-dioxygenase inhibitors, nutraceuticals, or physical exercise. Some researchers point out that beyond being activated during the disease, enteric glial cells may contribute to the development of synucleinopathies. Thus, it is still necessary to further study these cells and their role in Parkinson's disease.

Keywords: Parkinson’s disease; enteric glial cells; enteric nervous system; myenteric plexus; α synuclein.

PMID: 38279293 DOI: 10.3390/ijms25021294