Pathogenesis of diabetic neuropathy from the point of view of Schwann cell abnormalities

Abstract

Various factors have been implicated in the pathogenesis of diabetic neuropathy, such as polyol pathway hyperactivity, abnormal protein kinase C activity, increased oxidative stress, increased nonenzymatic glycation, and reduced synthesis of neurotrophic factors. C-peptide deficiency is also involved in the pathogenesis of diabetic neuropathy in type 1 diabetes. These glucose-mediated metabolic abnormalities affect all cellular components of nerve tissue including Schwann cells, neurons, and endoneurial endothelial cells. In diabetes, Schwann cells themselves undergo hyperglycemia insults, and the supporting functions of Schwann cells for neurons are also disturbed by high glucose, resulting in dysfunction of both neurons and Schwann cells. Among the treatments that are based on pathogenic mechanisms of diabetic neuropathy, medications such as α-lipoic acid, benfotiamine, actovegin, and epalrestat are available for clinical use. However, the efficacy of these agents is limited and unsatisfactory. The precise mechanism of action of each pathogenic factor and the interaction of these factors remain unknown. Therefore, the pathophysiological mechanisms should be elucidated for all cellular components of nerve tissue, including Schwann cells. Elucidation of the pathogenesis of diabetic neuropathy is essential for establishing effective treatment for this neuropathy.