Polymyxin B accelerates the α-synuclein aggregation

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons. It is characterised by the deposition of insoluble α-synuclein aggregates in the brain. Constipation is a common PD-associated condition, and the treatment of constipation with certain antibiotics seem to improve the PD symptoms. Polymyxin B, a last resort drug in treating the life-threatening Gram-negative bacterial infections, is one such antibiotic. The administration of polymyxin B in PD patients is known to alleviate the movement disorder symptoms; the mechanism of action, however, remains unclear. We, therefore, wondered if polymyxin B could modulate the aggregation of α-synuclein. We find that the polymyxin B catalyses the aggregation of α-synuclein into amyloid fibrils. At equimolar polymyxin B concentration, the lag phase was reduced to around one-third of that in the absence of polymyxin B.