Title:Targeting T Cell Metabolism as a Novel Approach for Treatment of MS:
With a Focus on PFKFB3 Inhibitors
Volume: 23
Issue: 4
Author(s): Mahsa Eshkevar Vakili, Fateme Nezhad Shah Mohammadi, Mohammad Reza Ataollahi, Keivan Shams, Kari K. Eklund, Gholamreza Daryabor and Kurosh Kalantar*
Affiliation:
- Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Autoimmune Diseases Research Center, Shiraz
University of Medical Sciences, Shiraz, Iran
Keywords:
Multiple sclerosis, autoimmunity, inflammation, TH17 cells, glycolysis, PFFKB3.
Abstract: Multiple sclerosis (MS) is one of the organ-specific autoimmune diseases in which
immune cells invade the neurons in the central nervous system (CNS) due to loss of tolerance
to self-antigens. Consequently, inflammation and demyelination occur in the central nervous
system. The pathogenesis of MS is not completely understood. However, it seems that T cells,
especially Th17 cells, have an important role in disease development. In recent years, studies
on the manipulation of metabolic pathways with therapeutic targets have received increasing
attention and have had promising results in some diseases, such as cancers. Glycolysis is a
central metabolic pathway and plays an important role in the differentiation of T CD4+ cells to
their subsets, especially Th17 cells. This suggests that manipulation of glycolysis, for example,
using appropriate safe inhibitors of this pathway can represent a means to affect the differentiation
of T CD4+, thus reducing inflammation and disease activity in MS patients. Hence, in
this study, we aimed to discuss evidence showing that using inhibitors of 6-phosphofructo-2-
kinase/fructose-2,6-biphosphatase 3(PFKFB3) as the main regulator of glycolysis may exert
beneficial therapeutic effects on MS patients.
