Dimethyl fumarate downregulates the immune response through the HCA2 /GPR109A pathway: Implications for the treatment of multiple sclerosis

Multiple Sclerosis and Related Disorders
Felipe von GlehnLeonilda M B Santos

Abstract

The mechanisms of action of dimethyl fumarate (DMF), and its metabolite, monomethyl fumarate (MMF), for the treatment of multiple sclerosis are not completely elucidated. To discuss the role of DMF/MMF-induced hydroxycarboxylic acid receptor 2 (HCA2/GPR109A) pathway activation in the immune response and treatment of MS. A narrative (traditional) review of the current literature. Studies have shown that binding of DMF/MMF to HCA2 on dendritic cells inhibits the production of pro-inflammatory cytokines in vitro and in MS murine models. Evidence suggests that activation of HCA2 expressed in immune cells and gut epithelial cells by DMF/MMF, may induce anti-inflammatory responses in the intestinal mucosa. Although the DMF/MMF mechanism of action remains unclear, evidence suggests that the activation of HCA2/GPR109A pathway downregulates the immune response and may activate anti-inflammatory response in the intestinal mucosa, possibly leading to reduction in CNS tissue damage in MS patients.

Citations

May 16, 2019·Neurology. Neuroimmunology and Neuroinflammation·Arie R GafsonPaul M Matthews
Aug 19, 2020·Multiple Sclerosis : Clinical and Laboratory Research·Allison Lm JordanYang Mao-Draayer
Nov 12, 2018·Auto- Immunity Highlights·Georgios K VasileiadisGeorgios M Hadjigeorgiou
Aug 10, 2019·Oxidative Medicine and Cellular Longevity·Natalia Robledinos-AntónAntonio Cuadrado
Feb 13, 2020·Frontiers in Oncology·Paul DentJohn F Hancock
Oct 23, 2020·Pharmacology & Therapeutics·Cinzia Dello RussoMunir Pirmohamed
Dec 31, 2020·Pharmaceuticals·Cara A Timpani, Emma Rybalka
Aug 25, 2021·Transplantation Proceedings·Xu ZhenLiang Sudong

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