Exploiting the Therapeutic Potential of Endogenous Immunomodulatory Systems in Multiple Sclerosis-Special Focus on the Peroxisome Proliferator-Activated Receptors (PPARs) and the Kynurenines.

摘要: Multiple sclerosis (MS) is a progressive neurodegenerative disease, characterized by autoimmune central nervous system (CNS) demyelination attributable to disturbed balance between encephalitic T helper 1 (Th1) and 17 (Th17) immunomodulatory regulatory cell (Treg) 2 (Th2) cells, an alternatively activated macrophage (M2) excess. Endogenous molecular systems regulating these inflammatory processes have recently been investigated identify molecules that can potentially influence the course of disease. These include peroxisome proliferator-activated receptors (PPARs), PPARγ coactivator-1alpha (PGC-1α), kynurenine pathway metabolites. Although all PPARs ameliorate experimental encephalomyelitis (EAE), recent evidence suggests PPARα, PPARβ/δ agonists less pronounced effects and, along with PGC-1α, are not biomarkers neuroinflammation in contrast PPARγ. Small clinical trials published positive results. Proposed as neuroprotective, therapeutic use PGC-1α activation needs be assessed EAE/MS. The indolamine 2,3-dioxygenase (IDO), rate-limiting step tryptophan (Trp) metabolism, plays crucial roles. Indeed, Trp metabolites relevance EAE drugs structural analogy kynurenines, such teriflunomide, already approved for MS. Further studies required gain deeper knowledge endogenous pathways potential implications