title: NADPH oxidase in brain injury and neurodegenerative disorders.
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.
authors.affiliation: Charlie Norwood VA Medical Center, One Freedom Way, Augusta, GA, 30904, USA.|Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, 1120 Fifteenth Street, Augusta, GA, 30912, USA.
authors.forename: Merry W
authors.initials: MW
authors.lastname: Ma
authors.affiliation: Charlie Norwood VA Medical Center, One Freedom Way, Augusta, GA, 30904, USA.|Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, 1120 Fifteenth Street, Augusta, GA, 30912, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Charlie Norwood VA Medical Center, One Freedom Way, Augusta, GA, 30904, USA.|Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, 1120 Fifteenth Street, Augusta, GA, 30912, USA.
authors.forename: Quanguang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Charlie Norwood VA Medical Center, One Freedom Way, Augusta, GA, 30904, USA.|Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, 1120 Fifteenth Street, Augusta, GA, 30912, USA.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Wang
authors.affiliation: Charlie Norwood VA Medical Center, One Freedom Way, Augusta, GA, 30904, USA.|Department of Neurosurgery, Medical College of Georgia, Augusta University, 1120 Fifteenth Street, Augusta, GA, 30912, USA.
authors.forename: Krishnan M
authors.initials: KM
authors.lastname: Dhandapani
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Health Science Center, 7703 Medical Drive, San Antonio, TX, 78229, USA.
authors.forename: Ratna K
authors.initials: RK
authors.lastname: Vadlamudi
authors.affiliation: Charlie Norwood VA Medical Center, One Freedom Way, Augusta, GA, 30904, USA. dbrann@augusta.edu.|Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, 1120 Fifteenth Street, Augusta, GA, 30912, USA. dbrann@augusta.edu.
authors.forename: Darrell W
authors.initials: DW
authors.lastname: Brann
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000201:enzymology*; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000201:enzymology*
chemical_list: D019255:NADPH Oxidases
keywords: Alzheimer’s disease; Amyotrophic lateral sclerosis; Huntington’s disease; Multiple sclerosis; NADPH oxidase; Neurodegeneration; Oxidative stress; Parkinson’s disease; Stroke; Traumatic brain injury