Anitha Suram, Chitra Venugopal, Annamalai Prakasam and Kumar Sambamurti Pages 365 - 375 ( 11 )
Alzheimers disease (AD) is a complex neurodegenerative disorder pathologically identified by the presence of extracellular senile plaques (SP) with a proteinaceous core composed of aggregates of the amyloid peptide (Aβ) and intracellular aggregates of the microtubule-associated protein tau (τ) as neurofibrillary tangles (NFTs). These hallmarks consist of abnormally folded proteinaceous components that are believed to be neurotoxic in AD. The mechanisms of toxicity remain unclear although oxidative stress and inflammation are implicated as mediators of the toxicity and these lesions, in turn, are known to damage cellular components including proteins, lipids in the membrane and DNA. However effects on genotoxicity and its role in AD are less clear. The present review discusses various influences, in particular of amyloid, on the genetic material and their possible role in the neurodegeneration in AD. Further, the amalgamation of genomics and proteomics in understanding AD and therapeutic development is suggested.
Alzheimer's disease, mutations, amyloid beta, DNA damage, 8OHdG, gene expression, cell cycle, p53
Medical University of South Carolina, Department of Neurosciences&The Center on Aging, 173 Ashley Avenue, BSB 403, Charleston, SC 29425, USA.