PHARMACOLOGICAL NEUROPROTECTION OF TYPE 1 DIABETES MELLITUS

Abstract

Type 1 diabetes mellitus (DM) - one of the most common diseases of modern endocrinology. The growing number of sick children, emergence of chronic diseases and high percentage of disability determine the severity of the problem. Diabetic neuropathy (DN), which occurs in more than half of patients with diabetes, often causes complications and mortality in patients with DM. Neuropathies cause the development of cognitive impairment. Clinical studies have shown that attention, memory, speed of assimilation of information and learning ability significantly worse in the type 1 DM. The main pathophysiological factor of DM assumes hyperglycemia that leads to dysfunction of polyol pathway of glucose metabolism, the accumulation of advanced glycation end products and mitogen-activated protein kinase, and changes in the activity of cyclooxygenase-2, Na + K + - ATPase, protein kinase C. Enhanced oxidation of glucose causes accumulation of reactive oxygen species (ROS). The development of diabetic neuropathy also is connected with activation of proinflammatory cytokines, which include Interleukin 1-p (IL-P), interleukin 6 (IL-6) and tumor necrosis factor (TNF a). These processes negative impact on neurons, causing their degeneration, segmental demyelination and violation of nerve impulses. Recent studies show that oxidative stress has a key role in apoptosis of neurons in patients with type 1 diabetes. Current treatment guidelines of DM have reduced its frequency, improved the quality of patients life, but did not solve the problem as a whole. Pharmacological properties of various antioxidant compounds of natural and synthetic origin (melatonin, N-acetylcysteine, alpha lipoic acid, bioflavanoyids, vitamins) in the treatment and prevention of DM are actively studying. It points to the possibilities of complex antioxidant treatment of diabetes complications, including DM. One of the areas of neuroprotection may be the induction of cytoprotective autophagy.

Keywords

• oxidative stress, apoptosis, autophagy, antioxidants.