Authors: Perry, George; Moreira, Paula I.; Santos, Maria S.; Oliveira, Catarina R.; Shenk, Justin C.; Nunomura, Akihiko; Smith, Mark A.; Zhu, Xiongwei

Source: CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets, Volume 7, Number 1, February 2008 , pp. 3-10(8)

Publisher: Bentham Science Publishers

Abstract:

Oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the pathologic hallmarks, neurofibrillary tangles and senile plaques. All classes of macromolecules (sugar, lipids, proteins, and nucleic acids) are affected by oxidative stress leading, inevitably, to neuronal dysfunction. Extensive data from the literature support the notion that mitochondrial and metal abnormalities are key sources of oxidative stress in Alzheimer disease. Furthermore, it has been suggested that in the initial stages of the development of Alzheimer disease, amyloid-β deposition and hyperphosphorylated tau function as compensatory responses to ensure that neuronal cells do not succumb to oxidative damage. However, during the progression of the disease, the antioxidant activity of both agents is either overwhelmed or, according to others, evolves into pro-oxidant activity resulting in the exacerbation of reactive species production.

Keywords: Alzheimer disease; antioxidant; chelator; iron; mitochondria; oxidative stress; reactive oxygen species

Document Type: Research article

DOI: http://dx.doi.org/10.2174/187152708783885156

Publication date: 2008-02-01

More about this publication?

• CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

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• In this Subject: Neurology & Psychiatry ,  Pharmacology
• By this author: Perry, George ;  Moreira, Paula I. ;  Santos, Maria S. ;  Oliveira, Catarina R. ;  Shenk, Justin C. ;  Nunomura, Akihiko ;  Smith, Mark A. ;  Zhu, Xiongwei

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