1: Med Hypotheses. 2001 Apr;56(4):472-7.

Therapeutic potential of N-acetylcysteine in age-related mitochondrial
neurodegenerative diseases.

Banaclocha MM.

Department of Pathology, Hospital La Paz, Madrid, Spain. marbanaci@latinmail.com

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. Copyright 2001 Harcourt
Publishers Ltd.

Publication Types:
Review

PMID: 11339849 [PubMed - indexed for MEDLINE]