NADPH oxidase in brain injury and neurodegenerative disorders

Merry W. Ma, Jing Wang, Quanguang Zhang, Ruimin Wang, Krishnan M. Dhandapani, Ratna K. Vadlamudi, Darrell W. Brann

Research output: Contribution to journalReview article

85 Citations (Scopus)

Abstract

Oxidative stress is a common denominator in the pathology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, as well as in ischemic and traumatic brain injury. The brain is highly vulnerable to oxidative damage due to its high metabolic demand. However, therapies attempting to scavenge free radicals have shown little success. By shifting the focus to inhibit the generation of damaging free radicals, recent studies have identified NADPH oxidase as a major contributor to disease pathology. NADPH oxidase has the primary function to generate free radicals. In particular, there is growing evidence that the isoforms NOX1, NOX2, and NOX4 can be upregulated by a variety of neurodegenerative factors. The majority of recent studies have shown that genetic and pharmacological inhibition of NADPH oxidase enzymes are neuroprotective and able to reduce detrimental aspects of pathology following ischemic and traumatic brain injury, as well as in chronic neurodegenerative disorders. This review aims to summarize evidence supporting the role of NADPH oxidase in the pathology of these neurological disorders, explores pharmacological strategies of targeting this major oxidative stress pathway, and outlines obstacles that need to be overcome for successful translation of these therapies to the clinic.

Original languageEnglish (US)
Article number7
JournalMolecular Neurodegeneration
Volume12
Issue number1
DOIs
StatePublished - Jan 17 2017

Fingerprint

NADPH Oxidase
Brain Diseases
Neurodegenerative Diseases
Brain Injuries
Pathology
Free Radicals
Oxidative Stress
Pharmacology
Huntington Disease
Amyotrophic Lateral Sclerosis
Nervous System Diseases
Multiple Sclerosis
Parkinson Disease
Alzheimer Disease
Protein Isoforms
Brain
Enzymes
Therapeutics
Traumatic Brain Injury

Keywords

  • Alzheimer's disease
  • Amyotrophic lateral sclerosis
  • Huntington's disease
  • Multiple sclerosis
  • NADPH oxidase
  • Neurodegeneration
  • Oxidative stress
  • Parkinson's disease
  • Stroke
  • Traumatic brain injury

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

NADPH oxidase in brain injury and neurodegenerative disorders. / Ma, Merry W.; Wang, Jing; Zhang, Quanguang; Wang, Ruimin; Dhandapani, Krishnan M.; Vadlamudi, Ratna K.; Brann, Darrell W.

In: Molecular Neurodegeneration, Vol. 12, No. 1, 7, 17.01.2017.

Research output: Contribution to journalReview article

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