Abstract
Multiple sclerosis is an inflammatory disease of the central nervous system, in which axonal transection takes place in parallel with acute inflammation to various, individual extents. The importance of the kynurenine pathway in the physiological functions and pathological processes of the nervous system has been extensively investigated, but it has additionally been implicated as having a regulatory function in the immune system. Alterations in the kynurenine pathway have been described in both preclinical and clinical investigations of multiple sclerosis. These observations led to the identification of potential therapeutic targets in multiple sclerosis, such as synthetic tryptophan analogs, endogenous tryptophan metabolites (e.g., cinnabarinic acid), structural analogs (laquinimod, teriflunomid, leflunomid and tranilast), indoleamine-2,3-dioxygenase inhibitors (1MT and berberine) and kynurenine-3-monooxygenase inhibitors (nicotinylalanine and Ro 61-8048). The kynurenine pathway is a promising novel target via which to influence the immune system and to achieve neuroprotection, and further research is therefore needed with the aim of developing novel drugs for the treatment of multiple sclerosis and other autoimmune diseases.
Highlights
Multiple sclerosis (MS) is a chronic disease with mainly inflammatory features in the beginning and later neurodegenerative processes take over
This means that such an inflammatory reaction is no longer reflected by contrast enhancement on magnetic resonance imaging (MRI), and drugs that target this type of inflammation should be able to enter the central nervous system (CNS) through an intact blood-brain barrier [2]
Experimental autoimmune encephalitis (EAE) is a T-cell-mediated autoimmune animal model for MS that is histologically similar to human MS [24,25]
Summary
Multiple sclerosis (MS) is a chronic disease with mainly inflammatory features in the beginning and later neurodegenerative processes take over. The blood-brain barrier damage observed with inflammation in the active white matter lesions in early MS differs in patients with progressive MS, in whom perivascular and parenchymal inflammation are seen, at least partly, in the absence of serum protein leakage from affected blood vessels. That such an inflammatory reaction is no longer reflected by contrast enhancement on MRI, and drugs that target this type of inflammation should be able to enter the CNS through an intact blood-brain barrier [2] Another pathological feature of progressive MS is cortical demyelination, which is probably one of the causes of the cognitive disability suffered by the patients [3,4]. While early relapsing and remitting disease is associated with the appearance of focal plaques in the white matter, cortical demyelination, and diffuse alterations of the white and gray matter are present in the progressive stage [2]
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