UNASSIGNED: Although the formation of beta-amyloid (Ab) deposits in the brain is a hallmark of @entity195 ( @entity195 ), the soluble oligomers rather than the mature amyloid fibrils most likely contribute to Ab @entity137 and @entity179 . Thus, the discovery of agents targeting soluble (Ab) oligomers is highly desirable for early diagnosis prior to the manifestation of a clinical @entity195 phenotype and also more effective therapies. We have previously reported that a novel 15 a.a peptide (15mer), isolated via phage display screening, targeted Ab and attenuated its @entity2359 (1). The aim of the current study was to generate and biochemically characterise analogues of this peptide with improved stability and therapeutic potential. We demonstrated that a stable analogue of the 15 a.a. peptide (15M S.A.) retained the activity and potency of the parent peptide and demonstrated improved proteolytic resistance in vitro (stable to t=300min c.f. t=30min for the parent peptide). This candidate reduced the formation of soluble Ab42 oligomers with the concurrent generation of non-toxic insoluble aggregates measuring up to 25-30 nm diameter as determined by atomic force microscopy. The 15M S.A. candidate directly interacted with oligomeric Ab42, as shown by coimmunoprecipitation and Surface Plasmon Resonance/Biacore analysis, with an affinity in the low micromolar range. Furthermore, this peptide bound fibrillar Ab42 and also stained plaques ex vivo in brain tissue from @entity195 model @entity19 . Given its multifaceted ability to target monomeric and aggregated Ab42 species, this candidate holds promise for novel preclinical @entity195 imaging and therapeutic strategies.

Validation and Characterisation of a Novel Peptide that Binds Monomeric and Aggregated Beta-amyloid and Inhibits the Formation of XXXX Oligomers.

@entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity179 :: ('MESH:D019636', 'Disease') :: ['neurodegeneration'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's Disease"] @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxicity']
@entity2359 :: (MESH:D020258,Disease) :: ['Neurotoxic']
