Rifampicin inhibits alpha-synuclein fibrillation and disaggregates fibrils - PubMed (original) (raw)

Rifampicin inhibits alpha-synuclein fibrillation and disaggregates fibrils

Jie Li et al. Chem Biol. 2004 Nov.

Abstract

The aggregation of alpha-synuclein in dopaminergic neurons of the substantia nigra is a critical step in the pathogenesis of Parkinson's disease. We show that the antibiotic rifampicin inhibited alpha-synuclein fibrillation and disaggregated existing fibrils in a concentration-dependent manner. Size-exclusion chromatography data indicated that rifampicin stabilized alpha-synuclein as both a monomer and soluble oligomers comprised of partially folded alpha-synuclein. Experiments using aged samples of rifampicin indicated that the most active species in inhibiting fibrillation and disaggregating fibrils is an oxidation product of rifampicin, which was confirmed in experiments under anaerobic conditions. These results indicate that rifampicin-mediated inhibition of alpha-synuclein fibrillation and disaggregation of fibrils involves preferential stabilization of monomeric and soluble oligomeric forms, and that rifampicin potentially may have therapeutic application for Parkinson's disease.

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Comment in

Targeting alpha-synuclein in Parkinson's disease.
Kapurniotu A. Kapurniotu A. Chem Biol. 2004 Nov;11(11):1476-8. doi: 10.1016/j.chembiol.2004.11.003. Chem Biol. 2004. PMID: 15555995

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Rifampicin inhibits alpha-synuclein fibrillation and disaggregates fibrils - PubMed (original) (raw)