Involvement of Free Radicals in the Development and Progression of Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is a major dementia related to an overproduction of free radicals (FRs), which leads to the generation of oxidative stress in brain tissue. Amyloid beta-peptide of 42 amino acid residues (Aβ 1-42) is the main source of FRs in patients with AD. βA 1-42 results from hydrolysis of the amyloid precursor protein by β-secretase in a process known as the amyloidogenic pathway. During βA 1-42 aggregation, the peptide interacts with various transition metals to produce hydrogen peroxide (H 2 O 2) by the Fenton reaction, generating the hydroxyl radical (• OH), which damages lipids, proteins, and nucleic acids, thereby contributing to neurodegeneration. In addition, βA 1-42 is recognized by microglial receptors; it activates these cells, causing overproduction of superoxide anion (O 2 •−) by NADPH oxidase; O 2 •− is also converted into H 2 O 2 and finally to • OH in the Fenton reaction. Other factors that contribute to oxidative stress during microglial activation are the overproduction of nitric oxide and interleukins and the overexpression of some enzymes, including cyclooxygenase and inducible nitric oxide synthase, all of which contribute to FR production. Currently, various models in vitro and in vivo exist that permit quantification of O 2 •− and H 2 O 2 and determination of the effects of these reactive oxygen species.

Current biomarkers and treatment strategies in Alzheimer disease: An overview and future perspectives

“…Other AD-related research show that group I mGluRs can control APP metabolism and hasten the conversion of APP into non-amyloidogenic APP( Chong et al, 2003 ). Additionally, it has been demonstrated that group III mGluR activation shields neurons from microglial neurotoxicity when Aβ is applied, which may be caused by the control of caspase activity( Hernández et al, 2016 );( Chong et al, 2005 ); ( Lin et al, 2001 ).…”