Role of enteric glia and microbiota-gut-brain axis in parkinson disease pathogenesis.

Claudino Dos Santos JC, Lima MPP, Brito GAC

Ageing Res Rev 2023

1. Ageing Res Rev. 2023 Feb;84:101812. doi: 10.1016/j.arr.2022.101812. Epub 2022 Nov 29. Role of enteric glia and microbiota-gut-brain axis in parkinson disease pathogenesis. Claudino Dos Santos JC(1), Lima MPP(2), Brito GAC(3), Viana GSB(4). Author information: (1)Medical School of the Christus University Center - UNICHRISTUS, Fortaleza, CE, Brazil; Graduate Program in Morphofunctional Sciences, Federal University of Ceará - UFC, Fortaleza, CE, Brazil. Electronic address: julio.santos@alu.ufc.br. (2)Medical School of the Christus University Center - UNICHRISTUS, Fortaleza, CE, Brazil. (3)Physiology and Pharmacology Department of the Federal University of Ceará - UFC, Fortaleza, CE, Brazil; Morphology Department of the Federal University of Ceará - UFC, Fortaleza, CE, Brazil. (4)Physiology and Pharmacology Department of the Federal University of Ceará - UFC, Fortaleza, CE, Brazil. The microbiota-gut-brain axis or simple gut-brain axis (GBA) is a complex and interactive bidirectional communication network linking the gut to the brain. Alterations in the composition of the gut microbiome have been linked to GBA dysfunction, central nervous system (CNS) inflammation, and dopaminergic degeneration, as those occurring in Parkinson's disease (PD). Besides inflammation, the activation of brain microglia is known to play a central role in the damage of dopaminergic neurons. Inflammation is attributed to the toxic effect of aggregated α-synuclein, in the brain of PD patients. It has been suggested that the α-synuclein misfolding might begin in the gut and spread "prion-like", via the vagus nerve into the lower brainstem and ultimately to the midbrain, known as the Braak hypothesis. In this review, we discuss how the microbiota-gut-brain axis and environmental influences interact with the immune system to promote a pro-inflammatory state that is involved in the initiation and progression of misfolded α-synuclein proteins and the beginning of the early