Does restraining nitric oxide biosynthesis rescue from toxins-induced parkinsonism and sporadic Parkinson's disease?

Mol Neurobiol. 2014 Feb;49(1):262-75. doi: 10.1007/s12035-013-8517-4. Epub 2013 Jul 31.

Abstract

Nitric oxide (NO) is an important inorganic molecule of the biological system owing to diverse physiological implications. NO is synthesised from a semi-essential amino acid L-arginine. NO biosynthesis is catalysed by a family of enzymes referred to as nitric oxide synthases (NOSs). NO is accused in many acute and chronic illnesses, which include central nervous system disorders, inflammatory diseases, reproductive impairments, cancer and cardiovascular anomalies. Owing to very unstable nature, NO gets converted into nitrite, peroxynitrite and other reactive nitrogen species that could lead to nitrosative stress in the nigrostriatal system. Nitrosative stress is widely implicated in Parkinson's disease (PD), and its beneficial and harmful effects are demonstrated in in vitro, rodent and primate models of toxins-induced parkinsonism and in the blood, cerebrospinal fluid and nigrostriatal tissues of sporadic PD patients. The current article updates the roles of NO and NOSs in sporadic PD and toxins-induced parkinsonism in rodents along with the scrutiny of how inhibitors of NOSs could open a new line of approach to moderately rescue from PD pathogenesis based on the existing literature. The article also provides a perspective concerning the lack of ample admiration to such an approach and how to minimise the underlying lacunae.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Methamphetamine / toxicity
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / physiology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Oxidopamine / toxicity
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / metabolism*
  • Parkinson Disease, Secondary / prevention & control
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / metabolism*
  • Reactive Nitrogen Species / antagonists & inhibitors
  • Reactive Nitrogen Species / metabolism*
  • Rotenone / toxicity

Substances

  • Reactive Nitrogen Species
  • Rotenone
  • Nitric Oxide
  • Methamphetamine
  • Oxidopamine
  • Nitric Oxide Synthase