Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice.
Article Details
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Zhu S, Stavrovskaya IG, Drozda M, Kim BY, Ona V, Li M, Sarang S, Liu AS, Hartley DM, Wu DC, Gullans S, Ferrante RJ, Przedborski S, Kristal BS, Friedlander RM
Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice.
Nature. 2002 May 2;417(6884):74-8.
- PubMed ID
- 11986668 [ View in PubMed]
- Abstract
Minocycline mediates neuroprotection in experimental models of neurodegeneration. It inhibits the activity of caspase-1, caspase-3, inducible form of nitric oxide synthetase (iNOS) and p38 mitogen-activated protein kinase (MAPK). Although minocycline does not directly inhibit these enzymes, the effects may result from interference with upstream mechanisms resulting in their secondary activation. Because the above-mentioned factors are important in amyotrophic lateral sclerosis (ALS), we tested minocycline in mice with ALS. Here we report that minocycline delays disease onset and extends survival in ALS mice. Given the broad efficacy of minocycline, understanding its mechanisms of action is of great importance. We find that minocycline inhibits mitochondrial permeability-transition-mediated cytochrome c release. Minocycline-mediated inhibition of cytochrome c release is demonstrated in vivo, in cells, and in isolated mitochondria. Understanding the mechanism of action of minocycline will assist in the development and testing of more powerful and effective analogues. Because of the safety record of minocycline, and its ability to penetrate the blood-brain barrier, this drug may be a novel therapy for ALS.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Minocycline Cytochrome c Protein Humans UnknownNegative modulatorDetails Minocycline Mitogen-activated Protein Kinases (Protein Group) Protein group Humans UnknownInhibitorDetails Minocycline Nitric oxide synthase, inducible Protein Humans UnknownInhibitorDetails