HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Mitochondrial disturbances, excitotoxicity, neuroinflammation and kynurenines: novel therapeutic strategies for neurodegenerative disorders.

Abstract
A mitochondrial dysfunction causes an abatement in ATP production, the induction of oxidative damage and the propagation of cell death pathways. It is additionally closely related to both glutamate excitotoxicity and neuroinflammation. All of these interconnected aspects of a cellular dysfunction are involved in the pathogenesis of numerous neurological disorders, including those with an acute (e.g. ischemic stroke) or a chronic (e.g. Huntington's disease) onset. Both acute and chronic neurodegenerative disorders have been demonstrated to involve multiple imbalances of the kynurenine pathway metabolism in the pathogenesis of the disease. As regards neuroactive compounds featuring in the pathway, quinolinic acid is a specific agonist of N-methyl-d-aspartate receptors, and a potent neurotoxin with additional and marked free radical-producing and lipid peroxidation-inducing properties. The toxic effects of 3-hydroxy-L-kynurenine are mediated by free radicals. Besides the possibility of increasing brain kynurenic acid concentrations, L-kynurenine may have vasoactive properties, too. Kynurenic acid has proven to be neuroprotective in several experimental settings, but in consequence of its pharmacokinetic properties it is not applicable as systemic administration in human cases. The aim of this short review is to emphasize the common features of cerebral ischemia and Huntington's disease and to highlight therapeutic strategies targeting the kynurenine pathway.
AuthorsDénes Zádori, Péter Klivényi, Levente Szalárdy, Ferenc Fülöp, József Toldi, László Vécsei
JournalJournal of the neurological sciences (J Neurol Sci) Vol. 322 Issue 1-2 Pg. 187-91 (Nov 15 2012) ISSN: 1878-5883 [Electronic] Netherlands
PMID22749004 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Kynurenine
Topics
  • Animals
  • Brain Ischemia (complications, metabolism, therapy)
  • Encephalitis (etiology, therapy)
  • Humans
  • Huntington Disease (complications, metabolism, therapy)
  • Kynurenine (metabolism, pharmacology, therapeutic use)
  • Mitochondria (drug effects, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: