title: Therapeutic potential of N-acetylcysteine in age-related mitochondrial neurodegenerative diseases.
abstract: Increasing lines of evidence suggest a key role for mitochondrial damage in neurodegenerative diseases. Brain aging, Parkinson's disease, Alzheimer's disease, Huntington's disease and Friedreich's ataxia have been associated with several mitochondrial alterations including impaired oxidative phosphorylation. Mitochondrial impairment can decrease cellular bioenergetic capacity, which will then increase the generation of reactive oxygen species resulting in oxidative damage and programmed cell death. This paper reviews the mechanisms of N-acetylcysteine action at the cellular level, and the possible usefulness of this antioxidant for the treatment of age-associated neurodegenerative diseases. First, this thiol can act as a precursor for glutathione synthesis as well as a stimulator of the cytosolic enzymes involved in glutathione regeneration. Second, N-acetylcysteine can act by direct reaction between its reducing thiol group and reactive oxygen species. Third, it has been shown that N-acetylcysteine can prevent programmed cell death in cultured neuronal cells. And finally, N-acetylcysteine also increases mitochondrial complex I and IV specific activities both in vitro and in vivo in synaptic mitochondrial preparations from aged mice. In view of the above, and because of the ease of its administration and lack of toxicity in humans, the potential usefulness of N-acetylcysteine in the treatment of age-associated mitochondrial neurodegenerative diseases deserves investigation.
authors.affiliation: Department of Pathology, Hospital La Paz, Madrid, Spain. marbanaci@latinmail.com
authors.forename: M M
authors.initials: MM
authors.lastname: Banaclocha
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000375:Aging / Q000473:pathology*; D006801:Humans; D008928:Mitochondria / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000111:Acetylcysteine