Chemokine CCL2 and Its Receptor CCR2 in Regulation of Cognitive Functions and in Development of Aging Diseases

摘要

Abstract Data are presented on a special group of cytokine proteins called chemokines, whose major and most important function is to stimulate the migration of leukocytes and other cells, thus they are involved in all protective, as well as destructive immune and inflammatory reactions. Chemokines mediate haptotaxis, chemokinesis, haptokinesis, adhesion, hematopoiesis, and angiogenesis. At the same time, chemokines release growth factors and cytokines and facilitate the regeneration of damaged tissues. One of the most important members of this group is the CCL2 chemokine which is able to regulate the infiltration and migration of various cells that play a significant role in non-specific and adaptive immunity, in inflammation and tissue regeneration, and in the activity of the central nervous system. The main receptor for CCL2 is CCR2 which is widely expressed in various cells and tissues. As a person ages, the content of CCL2 increases, which correlates with the development of severe cognitive impairment and the severity of diseases that occur most often in old age. It has been established that overexpression of CCL2 in the CNS contributes to an increase in pathogenic types of tau protein and is associated with glial neuroinflammatory changes. CCL2 and CCR2 are involved in altered amyloid beta (Aβ) metabolism which underlies Alzheimer’s disease. Increased expression of CCL2 in various areas of the CNS was found in Parkinson’s disease, depression, stroke, and traumatic brain injury, which correlates with manifestations of cognitive impairment. The CCL2/CCR2 axis plays a significant role in the pathogenesis of cardiovascular lesions, type 1 and type 2 diabetes mellitus, oncogenesis, and complications associated with atherosclerosis, including ischemic stroke, myocardial infarction, acute coronary syndrome, and severe heart failure. A significant increase in the level of CCL2 and the expression of CCR2 within tumor cells was found in cancer of various organs. Thus, CCL2 and CCR2 play a significant role in the development of age-related diseases.