ASSOCIATION BETWEEN OXIDATIVE STRESS AND MITOCHONDRIAL DYSFUNCTION IN PATIENTS WITH ALZHEIMER’S DISEASE AND TYPE II DIABETES

Abstract

The Type 2 Diabetes Mellitus (T2DM) and Alzheimer disease (AD) are two of the most common chronic diseases among aging populations in the majority of developed countries globally and are beginning to be considered biologically related disorders. Epidemiological data prove that patients with T2DM are at a very high risk of getting AD, which results in the newly emerged notion of Alzheimer’s disease as Type 3 Diabetes, which is a cerebral insulin resistance and brain glucose metabolism disruption. This review examines the common molecular pathways in which AD and T2DM comorbidity interact, focusing especially on oxidative stress and mitochondrial impairment as key actors of neurodegeneration. Overwhelming reactive oxygen species (ROS) production, mitochondrial bioenergetic dysfunction, calcium imbalances and insulin signal dysfunction have a vicious cycle that causes neuronal injury, amyloid-beta deposition and tau hyperphosphorylation to escalate. Also, oxidative stress, neuroinflammation, and impaired mitochondria are further amplified by advanced glycation end products (AGEs) and activation of the AGERAGE signaling axis. The review also discusses the role of disturbed mitochondrial dynamics, impaired mitophagy and neuroinflammatory reactions of microglia and astrocytes in progressive cognitive decline. New therapeutic approaches that address mitochondrial activity, oxidative stress, insulin resistance and metabolic homeostasis such as mitochondrial-targeted antioxidants, antidiabetic drugs, natural polyphenols and multi-target combination therapies are mentioned as potential remedies to disease pathology. Knowledge of the metabolicneurodegenerative interface of AD and T2DM is a crucial way to comprehend the pathogenesis of the disease, as well as to find new opportunities in early prevention, individual approach to treatment, and enhanced cognitive activity.