Article
 

Nitric oxide-mediated oxidative damage and the progressive demise of motor neurons in ALS

Public Deposited

Contenu téléchargeable

Télécharger le fichier PDF
https://ir.library.oregonstate.edu/concern/articles/t435gd68n

Descriptions

Attribute NameValues
Creator
Abstract
  • Oxidative damage is a common and early feature of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Dr. Mark Smith and his colleagues have built the case for oxidative stress being a primary progenitor rather than a secondary end-stage epiphenomenon of neurodegeneration. They proposed that reactive oxygen species contribute to the “age-related cascade of neurodegeneration” whereby accumulative oxidative damage with age promotes other characteristic pathological changes in afflicted brain regions, including protein aggregation, metabolic deficiencies, and inflammation. Nitric oxide (NO) likely plays a critical role in this age-related cascade. NO is a major signaling molecule produced in the central nervous system (CNS) to modulate neurological activity through stimulating cyclic GMP synthesis. However, the same physiological concentrations of NO relevant in cellular signaling may also initiate and amplify oxidative damage by diffusion-limited reactions with superoxide (O₂[superscript •−]) to produce peroxynitrite (ONOO⁻). This is perhaps best illustrated in ALS where physiological levels of NO promote survival of motor neurons, but the same concentrations can stimulate motor neuron apoptosis and glial cell activation under pathological conditions. While these changes represent a complex mechanism involving multiple cell types in the pathogenesis of ALS, they also reveal general processes underlying neurodegeneration.
  • Keywords: peroxynitrite, protein nitration, amyotrophic lateral sclerosis, nitric oxide, neurodegeneration
  • Keywords: peroxynitrite, protein nitration, amyotrophic lateral sclerosis, nitric oxide, neurodegeneration
Resource Type
DOI
Date Available
Date Issued
Citation
  • Drechsel, D., Estevez, A., Barbeito, L., & Beckman, J. (2012). Nitric oxide-mediated oxidative damage and the progressive demise of motor neurons in ALS. Neurotoxicity Research, 22(4), 251-264. doi: 10.1007/s12640-012-9322-y
Journal Title
Journal Volume
  • 22
Journal Issue/Number
  • 4
Academic Affiliation
Déclaration de droits
Funding Statement (additional comments about funding)
  • This work was financially supported in part by funding from the National Institute of Health grants NIEHS T32ES07060 & P30ES000210, NINDS R01NS058628A, and NCCAM P01AT002034, as well as support from the Amyotrophic Lateral Sclerosis Association (JSB).
Publisher
Peer Reviewed
Language
Replaces

Des relations

Parents:

This work has no parents.

Articles

La vignette Titre Date de téléchargement Visibilité actes
file details BeckmanJosephBiochemistryBiophysicsNitricOxideMediated.pdf 2017-07-10 Public Télécharger