The Role of Glutamate in the Pathogenesis of Multiple Sclerosis
- PDF / 147,806 Bytes
- 7 Pages / 594 x 792 pts Page_size
- 73 Downloads / 188 Views
The Role of Glutamate in the Pathogenesis of Multiple Sclerosis U. Sh. Kuzmina,1 L. F. Zainullina,1 V. A. Vakhitov,1 K. Z. Bakhtiyarova,2 and Yu. V. Vakhitova1
Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 119, No. 8, Iss. 1, pp. 160–167, August, 2019. Original article submitted July 12, 2018. Accepted September 11, 2018. Results from studies in recent years have provided evidence that hyperactivation of the glutamatergic system plays an important role in the pathophysiology of multiple sclerosis (MS). Apart from the well known immediate toxic effects of the neurotransmitter glutamate on neurons, additional mechanisms of glutamate-induced cell injury have been described, these including actions of oligodendrocytes, astrocytes, endothelial cells, and immune cells. These toxic effects may open up a link between the various pathological components of MS, such as axon damage, oligodendrocyte death, demyelination, autoimmune reactions, and dysfunction of the blood-brain barrier. Understanding the mechanisms underlying glutamate toxicity in MS may be promoted by the development of new approaches to the diagnosis, treatment, and management of patients with MS. This review presents reports on the mechanisms leading to increases in the concentration of the neurotransmitter glutamate and excitotoxicity in the context of the pathogenesis of the disease. We also present data on drugs and therapeutic approaches, both current and under development, helping to regulate the operation of the glutamatergic system. Keywords: glutamate, glutamate receptors, glutamate excitotoxicity, NMDA receptors, T cells, multiple sclerosis.
stance P, and others, which directly regulate the of proliferation, differentiation, apoptosis, and migration processes of immunocompetent cells [2]. It should be noted that the dysregulatory aspects of neuroimmunopathology are of significant interest, as impairments to the mechanisms of the interregulation of the nervous and immune systems cause or make important contributions to the pathogenesis of many neurodegenerative diseases of the CNS, especially diseases with autoimmune-inflammatory components and particularly multiple sclerosis (MS) [3]. Despite significant progress in studies of the pathogenesis of MS, the etiology of the disease remains unclear. The most widely held hypothesis is that MS is a multifactorial disease whose initiation and development involve a critical role for the interaction of genetic and environmental factors. This disease is characterized by the formation of inflammatory plaques in the white matter of the brain and/or spinal cord, with infiltration of immune cells, demyelination of nerve fibers, axon and neuron degeneration, oligodendrocyte death, astrogliosis, and damage to the blood-brain barrier (BBB) [4]. The gray matter of the brain is also involved in the pathogenesis of the disease, and while damage here is not accompanied by these features (presence of immune
A number of concepts of the bases of the interaction between the nervous and immun
Data Loading...
