Current Aging Science

Prof. Debomoy K. Lahiri
Department of Psychiatry Indiana University School of Medicine
Indianapolis, IN
USA

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Inhibition of Early Upstream Events in Prodromal Alzheimer’s Disease by Use of Targeted Antioxidants

Author(s): Kedar N. Prasad, Stephen C. Bondy.

Abstract:

A link between Alzheimer's disease (AD) and an excess presence of oxidant free radicals in the brain has frequently been reported. It is generally assumed that such oxidative stress and related cellular damage is caused by inflammatory changes in the brain and is consequent to amyloid deposition. This review makes the argument that elevated oxidative stress in AD is an early causal event in the initiation and advancement of this disease. Oxidative stress can be decreased by enhancing antioxidant enzymes through activation of the cytoplasmic transcriptional factor (Nrf2)/ARE (antioxidant response element) pathway, and by dietary and endogenous antioxidant chemicals. Reduction in the binding ability of Nrf2 to ARE lowers antioxidant enzyme levels. Decreased levels of Nrf2 and augmentation of oxidative stress in AD suggest that the ROS-dependent mechanism of activating the Nrf2/ARE pathway has become unresponsive. A combination of agents that can either activate the Nrf2-ARE pathway by ROS-independent mechanisms, or by acting directly as antioxidant chemicals, may be necessary to reduce oxidative stress in AD. Earlier shortcomings of using individual antioxidants may be due to consideration of antioxidants as pharmacological agents, ignoring the fact that individual antioxidants can be transmuted in the highly oxidant milieu that is present in AD. Interactions between various cellular compartments may require simultaneous examination of more than one agent. The clinical utility of such a more integrative method can reveal interactive effects such as those found in nutritional research and this can compensate for any mechanistic shortcomings of simultaneous testing of more than a single agent.

Keywords: Alzheimer's disease, antioxidants, free radicals, inflammation, neurodegenerative disease, oxidative stress.

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Article Details

VOLUME: 7
ISSUE: 2
Year: 2014
Page: [77 - 90]
Pages: 14
DOI: 10.2174/1874609807666140804115633
Price: $58