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International Journal of Cell Biology
Volume 2012, Article ID 391914, 13 pages
Review Article

Nitric Oxide Inactivation Mechanisms in the Brain: Role in Bioenergetics and Neurodegeneration

Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal

Received 27 March 2012; Accepted 18 April 2012

Academic Editor: Juan P. Bolaños

Copyright © 2012 Ricardo M. Santos et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


During the last decades nitric oxide (NO) has emerged as a critical physiological signaling molecule in mammalian tissues, notably in the brain. NO may modify the activity of regulatory proteins via direct reaction with the heme moiety, or indirectly, via S-nitrosylation of thiol groups or nitration of tyrosine residues. However, a conceptual understanding of how NO bioactivity is carried out in biological systems is hampered by the lack of knowledge on its dynamics in vivo. Key questions still lacking concrete and definitive answers include those related with quantitative issues of its concentration dynamics and diffusion, summarized in the how much, how long, and how far trilogy. For instance, a major problem is the lack of knowledge of what constitutes a physiological NO concentration and what constitutes a pathological one and how is NO concentration regulated. The ambient NO concentration reflects the balance between the rate of synthesis and the rate of breakdown. Much has been learnt about the mechanism of NO synthesis, but the inactivation pathways of NO has been almost completely ignored. We have recently addressed these issues in vivo on basis of microelectrode technology that allows a fine-tuned spatial and temporal measurement NO concentration dynamics in the brain.