Mitochondrial Disturbances, Tryptophan Metabolites and Neurodegeneration: Medicinal Chemistry Aspects

L.      Szalardy; P.      Klivenyi; D.      Zadori; F.      Fulop; J.      Toldi; L.      Vecsei

doi:10.2174/092986712800167365

Abstract

Neurodegenerative disorders, e.g. Parkinson’s, Huntington’s and Alzheimer’s diseases are distinct clinical and pathological entities sharing a number of leading features in their underlying processes. These common features involve the disturbances in the normal functioning of the mitochondria and the alterations in the delicate balance of tryptophan metabolism. The development of agents capable of halting the progression of these diseases is in the limelight of neuroscience research. This review highlights the role of mitochondria in the development of neurodegenerative processes with special focus on the involvement of neuroactive kynurenines both as pathological agents and potential targets and tools for future therapeutic approaches by providing a comprehensive summary of the main streams of rational drug design and giving an insight into present clinical achievements.

Keywords: Clinical trials, drug discovery, excitotoxicity, kynurenic acid, kynurenine system, mitochondria, neurodegeneration, neuroprotection, quinolic acid, tryptophan metabolism