tailieunhanh - Báo cáo khoa học: Modulation of a-synuclein aggregation by dopamine in the presence of MPTP and its metabolite

The neurotransmitter dopamine has been shown to inhibit fibrillation of a-synuclein by promoting the formation of nonamyloidogenic oligomers. Fibrillation ofa-synuclein is accelerated in the presence of pesticides and the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). | IFEBS Journal Modulation of a-synuclein aggregation by dopamine in the presence of MPTP and its metabolite Prashant N. Jethva Jay R. Kardani and Ipsita Roy Department of Biotechnology National institute of PharmaceuticalEducation and Research NIPER . Nagar India Keywords amyloid fibrillation Parkinson s disease synuclein thioflavin T Correspondence I. Roy Department of Biotechnology National institute of Pharmaceutical Education and Research NIPER Sector 67 . Nagar Punjab 160 062 India Fax 91 172 221 4692 Tel 91 172 229 2061 E-mail ipsita@ Received 28 September 2010 revised 24 February 2011 accepted 7 March 2011 doi The neurotransmitter dopamine has been shown to inhibit fibrillation of a-synuclein by promoting the formation of nonamyloidogenic oligomers. Fibrillation of a-synuclein is accelerated in the presence of pesticides and the neurotoxin 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine MPTP . The aim of this study was to determine whether dopamine continues to have an adverse effect on the fibrillation of a-synuclein in the presence of MPTP and its metabolite 1-methyl-4-phenylpyridinum ion MPP . We also attempted to answer the ambiguous question of whether conversion of MPTP to MPP is required for the fibrillation of a-synuclein. For this a-synuclein was incubated in the presence of MPTP and MPP along with dopamine. The fibrillation of a-synuclein was monitored by Thioflavin T fluorescence and immunoblotting. The morphology of the aggregates formed was observed using scanning electron microscopy. The concentrations of the neurotoxin and its metabolite were estimated by reverse phase HPLC. We found definitive evidence that the conversion of MPTP to MPP is not required for aggregation of a-synuclein. MPP was found to accelerate the rate of a-synuclein aggregation even in the absence of components of mitochondrial complex I. In contrast to the effect of dopamine on the aggregation of a-synuclein alone in the .