Rifampicin Inhibits -Synuclein Fibrillation and Disaggregates Fibrils

mentia development if they had been under antileprosy The aggregation of -synuclein in dopaminergic neutreatment with dapsone or rifampicin (Figure 1) and rons of the substantia nigra is a critical step in the closely related drugs for the preceding several years pathogenesis of Parkinson’s disease. We show that [22, 23]. For example, it has been shown that the overall the antibiotic rifampicin inhibited -synuclein fibrilprevalence of senile dementia was 2.9% in 1410 patients lation and disaggregated existing fibrils in a concenwho were continuously on antileprosy treatment, comtration-dependent manner. Size-exclusion chromapared with 6.25% in 1761 untreated patients [24]. Based tography data indicated that rifampicin stabilized on this observation, it has been suggested that some -synuclein as both a monomer and soluble oligomers drugs being used for leprosy might prevent A aggregacomprised of partially folded -synuclein. Experition, thus resulting in the absence of amyloid deposition ments using aged samples of rifampicin indicated that [25]. This hypothesis has been tested with two antilepthe most active species in inhibiting fibrillation and rosy drugs, depasone and rifampicin, and it has been disaggregating fibrils is an oxidation product of rifamfound that rifampicin and its analogs, p-benzoquinone picin, which was confirmed in experiments under anand hydroquinone, inhibited A 1-40 or A 1-42 aggregaaerobic conditions. These results indicate that rifampition and neurotoxicity in vitro [25–27]. Similar rifampicin cin-mediated inhibition of -synuclein fibrillation and effects have been recently reported for human islet amydisaggregation of fibrils involves preferential stabilizaloid polypeptide, amylin [26]. Rifampicin is a semisyntion of monomeric and soluble oligomeric forms, and thetic derivative of the rifamycins, a class of antibiotics that rifampicin potentially may have therapeutic applithat are fermentation products of Nocardia mediterranei cation for Parkinson’s disease. [28]. The common structure of rifamycins is a naphtho-