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Review
. 2009 Jul;118(1):131-50.
doi: 10.1007/s00401-009-0517-0. Epub 2009 Mar 14.

Oxidatively modified proteins in Alzheimer's disease (AD), mild cognitive impairment and animal models of AD: role of Abeta in pathogenesis

Rukhsana Sultana  1 , Marzia Perluigi, D Allan Butterfield
Affiliations
Review

Oxidatively modified proteins in Alzheimer's disease (AD), mild cognitive impairment and animal models of AD: role of Abeta in pathogenesis

Rukhsana Sultana et al. Acta Neuropathol. 2009 Jul.

Abstract

Oxidative stress has been implicated in the pathogenesis of a number of diseases including Alzheimer's disease (AD). The oxidative stress hypothesis of AD pathogenesis, in part, is based on beta-amyloid peptide (Abeta)-induced oxidative stress in both in vitro and in vivo studies. Oxidative modification of the protein may induce structural changes in a protein that might lead to its functional impairment. A number of oxidatively modified brain proteins were identified using redox proteomics in AD, mild cognitive impairment (MCI) and Abeta models of AD, which support a role of Abeta in the alteration of a number of biochemical and cellular processes such as energy metabolism, protein degradation, synaptic function, neuritic growth, neurotransmission, cellular defense system, long term potentiation involved in formation of memory, etc. All the redox proteomics-identified brain proteins fit well with the appearance of the three histopathological hallmarks of AD, i.e., synapse loss, amyloid plaque formation and neurofibrillary tangle formation and suggest a direct or indirect association of the identified proteins with the pathological and/or biochemical alterations in AD. Further, Abeta models of AD strongly support the notion that oxidative stress induced by Abeta may be a driving force in AD pathogenesis. Studies conducted on arguably the earliest stage of AD, MCI, may elucidate the mechanism(s) leading to AD pathogenesis by identifying early markers of the disease, and to develop therapeutic strategies to slow or prevent the progression of AD. In this review, we summarized our findings of redox proteomics identified oxidatively modified proteins in AD, MCI and AD models.

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Figures

Fig. 1
Fig. 1
Outline of redox proteomics approaches used in our laboratory for the identification of oxidatively modified brain proteins
Fig. 2
Fig. 2
The diagram shows the formation and consequences of amyloid beta-peptide in AD pathogenesis. APP represents amyloid precursor protein. See text for details
Fig. 3
Fig. 3
Venn diagram presents the functional categories of oxidatively modified brain proteins identified in AD, in MCI, and in common between the two disorders. See text for details
See this image and copyright information in PMC

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