Identification of amyloid-beta 1–42 binding protein fragments by screening of a human brain cDNA library

Extracellular and intraneuronal formation of amyloid-beta (Aβ) deposits have been demonstrated to be involved in the pathogenesis of Alzheimer's disease (AD). However, the precise mechanism of Aβ neurotoxicity is not completely understood. Previous studies suggest that binding of Aβ with a number of targets have deleterious effects on cellular functions. It has been shown that Aβ directly interacted with intracellular protein ERAB (endoplasmic reticulum amyloid β-peptide-binding protein) also known as ABAD (Aβ-binding alcohol dehydrogenase) resulting in mitochondrial dysfunction and cell death. In the present study we have identified another mitochondrial enzyme, ND3 of the human complex I, that binds to Aβ1–42 by the screening of a human brain cDNA library expressed on M13 phage. Our results indicated a strong interaction between Aβ and a phage-displayed 25 amino acid long peptide TTNLPLMVMSSLLLIIILALSLAYE corresponding to C-terminal peptide domain of NADH dehydrogenase, subunit 3 (MTND3) encoded by mitochondrial DNA (mtDNA). This interaction may explain, in part, the inhibition of complex I activity in astrocytes and neurons in the presence of Aβ, described recently. To our knowledge, the present study is the first demonstration of interaction between Aβ and one of the subunits of the human complex I.