Functions and dysfunctions of nitric oxide in brain

Biochim Biophys Acta Mol Basis Dis. 2019 Aug 1;1865(8):1949-1967. doi: 10.1016/j.bbadis.2018.11.007. Epub 2018 Nov 27.


Nitric oxide (NO) works as a retrograde neurotransmitter in synapses, allows the brain blood flow and also has important roles in intracellular signaling in neurons from the regulation of the neuronal metabolic status to the dendritic spine growth. Moreover NO is able to perform post-translational modifications in proteins by the S-nitrosylation of the thiol amino acids, which is a physiological mechanism to regulate protein function. On the other hand, during aging and pathological processes the behavior of NO can turn harmful when reacts with superoxide anion to form peroxynitrite. This gaseous compound can diffuse easily throughout the neuronal membranes damaging lipid, proteins and nucleic acids. In the case of proteins, peroxynitrite reacts mostly with the phenolic ring of the tyrosines forming nitro-tyrosines that affects dramatically to the physiological functions of the proteins. Protein nitrotyrosination is an irreversible process that also yields to the accumulation of the modified proteins contributing to the onset and progression of neurodegenerative processes such as Alzheimer's disease or Parkinson's disease.

Keywords: Alzheimer's disease; Glutamatergic signaling; Nitric oxide; Nitrosylation; Nitrotyrosine; Peroxynitrite.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Animals
  • Brain / metabolism*
  • Brain / physiopathology
  • Humans
  • Nitric Oxide / metabolism*
  • Nitrosative Stress
  • Oxidative Stress
  • Parkinson Disease / metabolism*
  • Parkinson Disease / physiopathology
  • Peroxynitrous Acid / metabolism
  • Protein Processing, Post-Translational
  • Proteins / metabolism


  • Proteins
  • Peroxynitrous Acid
  • Nitric Oxide