Amyloid-beta peptide binds to microtubule-associated protein 1B (MAP1B).
Extracellular and intraneuronal formation of amyloid-beta aggregates have been demonstrated to be involved in the pathogenesis of Alzheimer's disease. However, the precise mechanism of amyloid-beta neurotoxicity is not completely understood. Previous studies suggest that binding of amyloid-beta to a number of targets have deleterious effects on cellular functions. In the present study we have shown for the first time that amyloid-beta 1-42 bound to a peptide comprising the microtubule binding domain of the heavy chain of microtubule-associated protein 1B by the screening of a human brain cDNA library expressed on M13 phage. This interaction may explain, in part, the loss of neuronal cytoskeletal integrity, impairment of microtubule-dependent transport and synaptic dysfunction observed previously in Alzheimer's disease.
Gevorkian
Goar
G
Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Apartado Postal 70228, Cuidad Universitaria, Mexico DF, CP 04510, Mexico. gokar@servidor.unam.mx <gokar@servidor.unam.mx>
Gonzalez-Noriega
Alfonso
A
Acero
Gonzalo
G
Ordoñez
Jorge
J
Michalak
Colette
C
Munguia
Maria Elena
ME
Govezensky
Tzipe
T
Cribbs
David H
DH
Manoutcharian
Karen
K
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D045744:Cell Line, Tumor; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
D016229:Amyloid beta-Peptides; C475491:MAP1B protein, human; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D010455:Peptides; C075222:amyloid beta-protein (1-42)