Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain

Abstract

Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological data show that the incidence of AD increases with age and doubles every 5 years after 65 years of age. From a neuropathological point of view, amyloid-β-peptide (Aβ) leads to senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of AD. Aβ is associated with the formation of reactive oxygen (ROS) and nitrogen (RNS) species, and induces calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions associated with learning and memory. Oxidative stress was found to be associated with type 2 diabetes mellitus (T2DM), which (i) represents another prevalent disease associated with obesity and often aging, and (ii) is considered to be a risk factor for AD development. T2DM is characterized by high blood glucose levels resulting from increased hepatic glucose production, impaired insulin production and peripheral insulin resistance, which close resemble to the brain insulin resistance observed in AD patients. Furthermore, growing evidence suggest that oxidative stress play a pivotal role in the development of insulin resistance and vice versa. This review article provides molecular aspects and the pharmacological approaches from both preclinical and clinical data and interpreted from the point of view of oxidative stress with the aim to highlight progresses in this field.

Beneficial effects of anAndrographis paniculataextract and andrographolide on cognitive functions in streptozotocin-induced diabetic rats

“…Obesity and even pre-diabetes state are well-recognised risk factor for dementia and Alzheimer's disease (Gudala et al 2013;Butterfield et al 2014), and during recent years, suggestions have often made that structurally and functionally diverse secondary plant metabolites are potential therapeutic leads for prevention and cure of diabetes-associated dementia (Davinelli et al 2012;Recio et al 2012;Apetz et al 2014). By far a vast majority of such suggestive reports concentrate on plant polyphenolics with antioxidative properties, and a more recent report concludes that inhibition of acetylcholinesterase could also be involved in memory function improving effects of structurally diverse phytochemicals and plant polyphenolics (Huang et al 2013).…”

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

“…Decreases in enzymatic antioxidant defense capacity, including multiple superoxide dismutases (SOD), peroxiredoxins, and glutathione [103,104], further exacerbates oxidative damage [83,85,98,100]. Oxidative damage of multiple cellular components has been documented in both preclinical models of AD and in persons with the disease [102,105]. Key enzymes involved in mitochondrial function, such as PDH and α-ketoglutarate dehydrogenase, are often targeted by ROS, leading to deceased enzyme activity and decreased efficiency of mitochondrial electron transport (Fig.…”

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

“…Ample clinical and epidemiological studies suggest that patients with type 2 diabetes have a much greater risk of developing AD [117,118]. In animal models, both deficiency of insulin and insulin resistance lead to increased Aβ pathology.…”