Structural and kinetic analysis of protein-aggregate strains in vivo using binary epitope mapping

摘要: Despite considerable progress in uncovering the molecular details of protein aggregation vitro, cause and mechanism protein-aggregation disease remain poorly understood. One reason is that amount pathological aggregates neural tissue exceedingly low, precluding examination by conventional approaches. We present here a method for determination structure quantity small samples, circumventing above problem. The based on binary epitope mapping using anti-peptide antibodies. assessed usefulness versatility mice modeling neurodegenerative amyotrophic lateral sclerosis, which accumulate intracellular superoxide dismutase-1. Two strains were identified with different structural architectures, properties, growth kinetics. Both from dismutase-1 generated vitro under variety conditions. strains, seem kinetically fragmentation control, are associated progressions, complying adding detail to growing evidence seeding, infectivity, strain dependence unifying principles disease.