α-synuclein super-mutants accelerate α-synuclein aggregation
AssigneeAmgen Inc.
InventorsAnja Leona Biere, Martin Citron
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Abstract
Parkinson's disease (PD) is a neurodegenerative disorder which is pathologically characterized by the presence of intracytoplasmic Lewy bodies, the major component of which are filaments consisting of α-synuclein. The present invention provides α-synuclein mutations which accelerate α-synuclein aggregation and can thus be utilized for transgenic animal production and generation of the first progressive PD model. Also provided is an in vitro aggregation assay which can be utilized to identify α-synuclein nucleation inhibitors for the treatment of PD.
Claims5
An isolated artificial α-synuclein mutant polypeptide which demonstrates accelerated aggregation as compared to naturally occurring α-synuclein mutant polypeptides.
An in vitro aggregation assay for evaluating α-synuclein mutants which demonstrate accelerated aggregation, said assay comprising the steps of:
- (a) generating pure α-synuclein protein;
- (b) incubating the α-synuclein solution with defined agitation;
- (c) centrifuging aliquots of the incubated samples at predetermined times;
- and
- (4) analyzing the pellet and the supernatant of the aliquoted samples using various conventional techniques.
Dependencies are inferred from the claim text.