Identification of amyloid-beta 1-42 binding protein fragments by screening of a human brain cDNA library.
Extracellular and intraneuronal formation of amyloid-beta (Abeta) deposits have been demonstrated to be involved in the pathogenesis of Alzheimer's disease (AD). However, the precise mechanism of Abeta neurotoxicity is not completely understood. Previous studies suggest that binding of Abeta with a number of targets have deleterious effects on cellular functions. It has been shown that Abeta directly interacted with intracellular protein ERAB (endoplasmic reticulum amyloid beta-peptide-binding protein) also known as ABAD (Abeta-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 Abeta1-42 by the screening of a human brain cDNA library expressed on M13 phage. Our results indicated a strong interaction between Abeta 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 Abeta, described recently. To our knowledge, the present study is the first demonstration of interaction between Abeta and one of the subunits of the human complex I.
Munguia
Maria Elena
ME
Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), Apartado Postal 70228, Cuidad Universitaria, Mexico DF, CP 04510, Mexico.
Govezensky
Tzipe
T
Martinez
Rodrigo
R
Manoutcharian
Karen
K
Gevorkian
Goar
G
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015139:Blotting, Southern / Q000379:methods; D001921:Brain / Q000378:metabolism*; D053938:DNA Fragmentation / Q000502:physiology; D042967:Electron Transport Complex I; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015723:Gene Library; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011506:Proteins; C075222:amyloid beta-protein (1-42); D042967:Electron Transport Complex I; C114961:MT-ND3 protein, human