Oxidative Damage, Protein Synthesis, and Protein Degradation in Alzheimer's Disease

Authors: Ding, Qunxing; Dimayuga, Edgardo; Keller, Jeffrey N.

Source: Current Alzheimer Research, Volume 4, Number 1, February 2007 , pp. 73-79(7)

Publisher: Bentham Science Publishers

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Abstract:

A large number of studies has firmly established that increases in oxidative damage occurs in Alzheimer's disease (AD). Such studies have demonstrated that increased in oxidative damage selectively occurs within the brain regions involved in regulating cognitive performance. Studies from our laboratory and others have provided experimental evidence that increased levels of oxidative damage occur in subjects with Mild Cognitive Impairment (MCI), which is believed to be one of the earliest stages of AD, and is a condition which is devoid of dementia or the extensive neurofibrillary pathology and neuritic plaque deposition observed in AD. Together, these data support a role for the accrual of oxidative damage potentially serving as an early event that then initiates the development of cognitive disturbances and pathological features observed in AD. Recent studies from our laboratory have demonstrated that a decline in protein synthesis capabilities occurs in the same brain regions which exhibit increased levels of oxidative damage in MCI and AD subjects. The focus of this review is to describe the large number of studies which suggest protein synthesis may be one of the earliest cellular processes disrupted by oxidative damage in AD. Taken together, these findings have important implications for understanding the molecular and cellular basis of AD, understanding the basis for oxidative stress in AD, and may have important implications for studies involving proteomics and proteolysis in AD.

Keywords: Alzheimer's disease; lysosome; Mild Cognitive Impairment; oxidative stress; proteasome; protein synthesis; ribosome; RNA

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156720507779939788

Affiliations: 1: 205 Sanders-Brown Center on Aging, University of Kentucky, Lexington KY 40536-0230, USA.

Publication date: 2007-02-01

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Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.

Oxidative Damage, Protein Synthesis, and Protein Degradation in Alzheimer's Disease

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