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Review
. 2010 Jun;41(2-3):73-86.
doi: 10.1007/s12035-010-8107-7. Epub 2010 Mar 2.

Targeting NADPH oxidase and phospholipases A2 in Alzheimer's disease

Agnes Simonyi  1 , Yan He, Wenwen Sheng, Albert Y Sun, W Gibson Wood, Gary A Weisman, Grace Y Sun
Affiliations
Review

Targeting NADPH oxidase and phospholipases A2 in Alzheimer's disease

Agnes Simonyi et al. Mol Neurobiol. 2010 Jun.

Abstract

Alzheimer's disease (AD) is marked by an increase in the production of extracellular beta amyloid plaques and intracellular neurofibrillary tangles associated with a decline in brain function. Increases in oxidative stress are regarded as an early sign of AD pathophysiology, although the source of reactive oxygen species (ROS) and the mechanism(s) whereby beta amyloid peptides (Abeta) impact oxidative stress have not been adequately investigated. Recent studies provide strong evidence for the involvement of NADPH oxidase and its downstream oxidative signaling pathways in the toxic effects elicited by Abeta. ROS produced by NADPH oxidase activate multiple signaling pathways leading to neuronal excitotoxicity and glial cell-mediated inflammation. This review describes recent studies demonstrating the neurotoxic effects of Abeta in conjunction with ROS produced by NADPH oxidase and the downstream pathways leading to activation of cytosolic phospholipase A(2) (PLA(2)) and secretory PLA(2). In addition, this review also describes recent studies using botanical antioxidants to protect against oxidative damage associated with AD. Investigating the metabolic and signaling pathways involving Abeta NADPH oxidase and PLA(2) can help understand the mechanisms underlying the neurodegenerative effects of oxidative stress in AD. This information should provide new therapeutic approaches for prevention of this debilitating disease.

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Figures

Fig. 1
Fig. 1
The role of Aβ in the coupling of NADPH oxidase and NMDA receptor signaling pathways in neurons
Fig. 2
Fig. 2
Effects of Aβ on cytokine-induced inflammatory responses in glial cells: the role of NADPH oxidase
Fig. 3
Fig. 3
Chemical structures of some flavonoids described in Table 1
See this image and copyright information in PMC

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