Post-translational regulation of neuronal nitric oxide synthase: implications for sympathoexcitatory states

Neeru M. Sharma, Kaushik P. Patel

Research output: Contribution to journalReview article

7 Scopus citations

Abstract

Introduction: Nitric oxide (NO) synthesized via neuronal nitric oxide synthase (nNOS) plays a significant role in regulation/modulation of autonomic control of circulation. Various pathological states are associated with diminished nNOS expression and blunted autonomic effects of NO in the central nervous system (CNS) including heart failure, hypertension, diabetes mellitus, chronic renal failure etc. Therefore, elucidation of the molecular mechanism/s involved in dysregulation of nNOS is essential to understand the pathogenesis of increased sympathoexcitation in these diseased states. Areas covered: nNOS is a highly regulated enzyme, being regulated at transcriptional and posttranslational levels via protein-protein interactions and modifications viz. phosphorylation, ubiquitination, and sumoylation. The enzyme activity of nNOS also depends on the optimal concentration of substrate, cofactors and association with regulatory proteins. This review focuses on the posttranslational regulation of nNOS in the context of normal and diseased states within the CNS. Expert opinion: Gaining insight into the mechanism/s involved in the regulation of nNOS would provide novel strategies for manipulating nNOS directed therapeutic modalities in the future, including catalytically active dimer stabilization and protein-protein interactions with intracellular protein effectors. Ultimately, this is expected to provide tools to improve autonomic dysregulation in various diseases such as heart failure, hypertension, and diabetes.

Original languageEnglish (US)
Pages (from-to)11-22
Number of pages12
JournalExpert Opinion on Therapeutic Targets
Volume21
Issue number1
DOIs
StatePublished - Jan 2 2017

Keywords

  • Cardiovascular diseases
  • PVN
  • nNOS
  • sympathoexcitation

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Post-translational regulation of neuronal nitric oxide synthase: implications for sympathoexcitatory states'. Together they form a unique fingerprint.

  • Cite this