Role of A1 Adenosinergic System in Multiple Sclerosis and Possible Therapeutic Strategy

Abstract

Multiple sclerosis (MS) is one of the most affecting autoimmune neurodegenerative disease characterized by chronic neuroinflammation, demyelination and impaired neuronal conduction. The oligodendrocytes toxicity by inflammatory cytokines and oxy-radicals are considered to be the most important factor in demyelination of motor neurons. The dysfunction of neuronal A1 adenosine receptor (A1AR) contributes to the demyelination of neurons by triggering the pro-inflammatory cytokines, oxy-radicals and neuroinflammatory cascades. In MS pathogenesis, Antigen presenting cells, MHC protein, CD4+T-cells, GM-CSF along with effector cells enhance the activation of macrophages in adenosinergic declined conditions, where it shows cumulative effects which leads to oligodendrocytes toxicity and demyelination of motor neurons. In general, A1AR is mainly expressed in macrophage lineage cells in central nervous system which could control the macrophage activation upon stimulation by its agonists. In this review, we have mainly emphasized on the pathogenesis of MS and highlighted the importance of adenosinergic system in reversing the molecular events in MS. In addition, we have discussed about the beneficial role of A1AR agonists in MS management.