Abstract
The elucidation of the intriguing relationship between oxidative stress and Alzheimer’s disease is crucial to understand the pathogenesis of the disease as also to design a suitable drug trial with antioxidants against this condition. We begin by reviewing the basic facts about Alzheimer’s disease and the chemistry and biology of oxygen free radicals with particular reference to the cellular adaptive response through redox-signalling pathways. The post-mortem evidence of oxidative damage in the brain of Alzheimer’s disease patients is overwhelming which is also supported by the similar changes in transgenic mice models of this disease. However, the causal relationship of oxidative stress with amyloid beta pathology or the genesis of Alzheimer’s disease is not clear. Considering the available evidence the review suggests that the oxidative stress could be an early event in the disease process and may trigger various adaptive responses such as the alterations of amyloid beta metabolism and the activation of stress responsive kinases which can subsequently lead to neuronal degeneration and AD pathology. Further, we have presented a large body of evidence from various studies to highlight the beneficial effects of antioxidants against amyloid beta toxicity or AD pathology in animal or cell based models of AD. The failure of clinical trials with antioxidants against AD has been mentioned and the possible causes of such failures have been analysed.
Keywords: Alzheimer’s disease, amyloid beta protein, oxidative stress, antioxidant, redox signalling, lipid peroxidation, protein oxidation, DNA damage.
Current Medicinal Chemistry
Title:Oxidative Stress and Amyloid Beta Toxicity in Alzheimer’s Disease: Intervention in a Complex Relationship by Antioxidants
Volume: 20 Issue: 37
Author(s): S. Chakrabarti, M. Sinha, I. G. Thakurta, P. Banerjee and M. Chattopadhyay
Affiliation:
Keywords: Alzheimer’s disease, amyloid beta protein, oxidative stress, antioxidant, redox signalling, lipid peroxidation, protein oxidation, DNA damage.
Abstract: The elucidation of the intriguing relationship between oxidative stress and Alzheimer’s disease is crucial to understand the pathogenesis of the disease as also to design a suitable drug trial with antioxidants against this condition. We begin by reviewing the basic facts about Alzheimer’s disease and the chemistry and biology of oxygen free radicals with particular reference to the cellular adaptive response through redox-signalling pathways. The post-mortem evidence of oxidative damage in the brain of Alzheimer’s disease patients is overwhelming which is also supported by the similar changes in transgenic mice models of this disease. However, the causal relationship of oxidative stress with amyloid beta pathology or the genesis of Alzheimer’s disease is not clear. Considering the available evidence the review suggests that the oxidative stress could be an early event in the disease process and may trigger various adaptive responses such as the alterations of amyloid beta metabolism and the activation of stress responsive kinases which can subsequently lead to neuronal degeneration and AD pathology. Further, we have presented a large body of evidence from various studies to highlight the beneficial effects of antioxidants against amyloid beta toxicity or AD pathology in animal or cell based models of AD. The failure of clinical trials with antioxidants against AD has been mentioned and the possible causes of such failures have been analysed.
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Chakrabarti S., Sinha M., Thakurta G. I., Banerjee P. and Chattopadhyay M., Oxidative Stress and Amyloid Beta Toxicity in Alzheimer’s Disease: Intervention in a Complex Relationship by Antioxidants, Current Medicinal Chemistry 2013; 20 (37) . https://dx.doi.org/10.2174/09298673113209990152
DOI https://dx.doi.org/10.2174/09298673113209990152 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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