Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1865, Issue 8, Pages 1949-1967Publisher
ELSEVIER
DOI: 10.1016/j.bbadis.2018.11.007
Keywords
Nitric oxide; Glutamatergic signaling; Nitrosylation; Peroxynitrite; Nitrotyrosine; Alzheimer's disease
Funding
- Spanish Ministry of Economy and Business [SAF2017-83372-R, MDM-2014-0370]
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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.
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