Potential Glioprotective Strategies Against Diabetes-Induced Brain Toxicity

Astrocytes are crucial for the maintenance of brain homeostasis by actively participating in the metabolism of glucose, which is the main energy substrate for the central nervous system (CNS), in addition to other supportive functions. More specifically, astrocytes support neurons through the metabolic coupling of synaptic activity and glucose utilization. As such, diabetes mellitus (DM) and consequent glucose metabolism disorders induce astrocyte damage, affecting CNS functionality. Glioprotective molecules can promote protection by improving glial functions and avoiding toxicity in different pathological conditions, including DM. Therefore, this review discusses specific pathomechanisms associated with DM/glucose metabolism disorder-induced gliotoxicity, namely astrocyte metabolism, redox homeostasis/mitochondrial activity, inflammation, and glial signaling pathways. Studies investigating natural products as potential glioprotective strategies against these deleterious effects of DM/glucose metabolism disorders are also reviewed herein. These products include carotenoids, catechins, isoflavones, lipoic acid, polysaccharides, resveratrol, and sulforaphane.