Design and Experimental Evaluation of a Peptide Antagonist against Amyloid β(1-42) Interactions with Calmodulin and Calbindin-D28k.

ABSTRACT: Amyloid β_1-42 (Aβ(1-42)) oligomers have been linked to the pathogenesis of Alzheimer's disease (AD). Intracellular calcium (Ca²⁺) homeostasis dysregulation with subsequent alterations of neuronal excitability has been proposed to mediate Aβ neurotoxicity in AD. The Ca²⁺ binding proteins calmodulin (CaM) and calbindin-D28k, whose expression levels are lowered in human AD brains, have relevant roles in neuronal survival and activity. In previous works, we have shown that CaM has a high affinity for Aβ(1-42) oligomers and extensively binds internalized Aβ(1-42) in neurons. In this work, we have designed a hydrophobic peptide of 10 amino acid residues: VFAFAMAFML (amidated-C-terminus amino acid) mimicking the interacting domain of CaM with Aβ (1-42), using a co

SUBMITTER: Salazar J 

PROVIDER: S-EPMC8880779 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature