Oxidative stress in Alzheimer disease

Abstract

Alzheimer disease (AD) is a progressive dementia affecting a large proportion of the aging population. The histopathological changes in AD include neuronal cell death, formation of amyloid plaques and neurofibrillary tangles. There is also evidence that brain tissue in patients with AD is exposed to oxidative stress (e.g., protein oxidation, lipid oxidation, DNA oxidation and glycoxidation) during the course of the disease. Advanced glycation endproducts (AGEs) are present in amyloid plaques in AD, and its extracellular accumulation may be caused by an accelerated oxidation of glycated proteins. AGEs participate in neuronal death causing direct (chemical) and indirect (cellular) free radical production and consequently increase oxidative stress. The development of drugs for the treatment of AD that breaks the vicious cycles of oxidative stress and neurodegeneration offer new opportunities. These approaches include AGE-inhibitors, antioxidants and anti-inflammatory substances, which prevent free radical production.

Oxidative Stress and β-Amyloid Protein in Alzheimer’s Disease

“…Over the past decade, extensive oxidative research has been performed on the pathogenesis of AD (Ansari and Scheff 2010;Gella and Durany 2009;Gibson et al 1999;Srikanth et al 2011). A number of factors may account for increased vulnerability to oxidative stress and damage in AD.…”

Analyzing Nootropic Effect of <i>Phyllanthus reticulatus</i> Poir. on Cognitive Functions, Brain Antioxidant Enzymes and Acetylcholinesterase Activity against Aluminium-Induced Alzheimer’s Model in Rats: Applicable for Controlling the Risk Factors of Alzheimer’s Disease

“…The greatest marked DNA adduct defined is 8-hydroxy-2-deoxyguanosine (8-OHdG) [26]. On the other hand advanced glycation end products are produced due to posttranslational modifications of proteins and may play a role in AD that is connected to oxidative modifications of Aβ peptides and tau [27]. In addition to this, the brain is largely composed of easily oxidized lipids, has a high oxygen consumption rate, high metabolic rate of transitional metals and lacks strong antioxidant defenses, that's why it is quite vulnerable to oxidative injury [28].…”

Dehydroepiandrosterone (DHEA) and DHEA Sulfate: Roles in Brain Function and Disease

“…It is also supported by the demonstration that oxidative stress associated with the presence of β-amyloid treatment induces DHEA synthesis in human and rodent cells in vitro [126][127][128][129]. In this context, it is interesting that the brain regions containing the higher concentrations of DHEA [126] also have higher burdens of neuritic plaques and β-amyloid immunoreactivity, features that are generally associated with AD progression [130]. It may be significant that DHEA protects HT-22 cells (an immortalized mouse hippocampal cell line) against amyloid β protein toxicity in a dose-dependent manner [131].…”