A Systematic Review on the Role of Arachidonic Acid Pathway in Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease characterized by destruction of oligodendrocytes, immune cell infiltration and demyelination. Inflammation plays a significant role in MS, and the inflammatory mediators such as eicosanoids, leukotrienes, and superoxide radicals are involved in pro-inflammatory responses in MS. In this systematic review, we tried to define and discuss all the findings of in vivo animal studies and human clinical trials on the potential association between arachidonic acid (AA) pathway and multiple sclerosis.

A systematic literature search across Pubmed, Scopus, Embase and Cochrane database was conducted. This systematic review was performed according to PRISMA guidelines.

A total of 146 studies were included, of which 34 were conducted on animals, 58 on humans, and 60 studies reported the role of different compounds that target AA mediators or their corresponding enzymes/receptors, and can have a therapeutic effect in MS. These results suggest that eicosanoids have significant roles in Experimental Autoimmune Encephalomyelitis (EAE) and MS. The data from animal and human studies elucidated that PGI₂, PGFI_2α, PGDI₂, isoprostanes, PGEI₂, PLAI₂, and LTs are increased in MS. PLAI₂ inhibition modulates the progression of the disease. PGE1 analogues can be a useful option in the treatment of MS.

All studies reported the beneficial effects of COX and LOX inhibitors in MS. The hybrid compounds, such as COX-2 inhibitors/TP antagonists and 5-LOX inhibitors, can be an innovative approach for multiple sclerosis treatment. Future work in MS should shed light on synthesizing new compounds targeting the arachidonic acid pathway.