NADPH oxidase as a therapeutic target in Alzheimer's disease

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

At present, available treatments for Alzheimer's disease (AD) are largely unable to halt disease progression. Microglia, the resident macrophages in the brain, are strongly implicated in the pathology and progressively degenerative nature of AD. Specifically, microglia are activated in response to both β amyloid (Aβ) and neuronal damage, and can become a chronic source of neurotoxic cytokines and reactive oxygen species (ROS). NADPH oxidase is a multi-subunit enzyme complex responsible for the production of both extracellular and intracellular ROS by microglia. Importantly, NADPH oxidase expression is upregulated in AD and is an essential component of microglia-mediated Aβ neurotoxicity. Activation of microglial NADPH oxidase causes neurotoxicity through two mechanisms: 1) extracellular ROS produced by microglia are directly toxic to neurons; 2) intracellular ROS function as a signaling mechanism in microglia to amplify the production of several pro-inflammatory and neurotoxic cytokines (for example, tumor necrosis factor-α, prostaglandin E2, and interleukin-1β). The following review describes how targeting NADPH oxidase can reduce a broad spectrum of toxic factors (for example, cytokines, ROS, and reactive nitrogen species) to result in inhibition of neuronal damage from two triggers of deleterious microglial activation (Aβ and neuron damage), offering hope in halting the progression of AD.

Original languageEnglish (US)
Article numberS8
JournalBMC Neuroscience
Volume9
Issue numberSUPPL. 2
DOIs
StatePublished - Dec 3 2008
Externally publishedYes

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NADPH Oxidase
Microglia
Alzheimer Disease
Reactive Oxygen Species
Poisons
Cytokines
Hope
Therapeutics
Neurons
Reactive Nitrogen Species
Interleukin-1
Dinoprostone
Amyloid
Disease Progression
Tumor Necrosis Factor-alpha
Macrophages
Pathology
Brain
Enzymes

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)

Cite this

NADPH oxidase as a therapeutic target in Alzheimer's disease. / Block, Michelle.

In: BMC Neuroscience, Vol. 9, No. SUPPL. 2, S8, 03.12.2008.

Research output: Contribution to journalArticle

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