Targeting NADPH oxidase and phospholipases A2 in alzheimer's disease

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

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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 (Aβ) 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 Aβ. 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 Aβ in conjunction with ROS produced by NADPH oxidase and the downstream pathways leading to activation of cytosolic phospholipase A2 (PLA2) and secretory PLA2. 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 Aβ NADPH oxidase and PLA2 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.

Original languageEnglish (US)
Pages (from-to)73-86
Number of pages14
JournalMolecular neurobiology
Volume41
Issue number2-3
DOIs
StatePublished - Jun 2010

Keywords

  • Astrocytes
  • Botanical phenols
  • Cytosolic phospholipase A
  • ERK1/2
  • Microglial cells
  • NADPH oxidase
  • Neurons
  • Secretory phospholipase A

Fingerprint Dive into the research topics of 'Targeting NADPH oxidase and phospholipases A<sub>2</sub> in alzheimer's disease'. Together they form a unique fingerprint.

Cite this