The alpha5beta1 integrin mediates elimination of amyloid-beta peptide and protects against apoptosis.
The amyloid-beta peptide (Abeta) can mediate cell attachment by binding to beta1 integrins through an arg-his-asp sequence. We show here that the alpha5beta1 integrin, a fibronectin receptor, is an efficient binder of Abeta, and mediates cell attachment to nonfibrillar Abeta. Cells engineered to express alpha5beta1 internalized and degraded more added Abeta1-40 than did alpha5beta1-negative control cells. Deposition of an insoluble Abeta1-40 matrix around the alpha5beta1-expressing cells was reduced, and the cells showed less apoptosis than the control cells. Thus, the alpha5beta1 integrin may protect against Abeta deposition and toxicity, which is a course of Alzheimer's disease lesions.
Matter
M L
ML
La Jolla Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA.
Zhang
Z
Z
Nordstedt
C
C
Ruoslahti
E
E
D016229:Amyloid beta-Peptides / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016466:CHO Cells; D002448:Cell Adhesion; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D009447:Neuroblastoma; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D017469:Receptors, Fibronectin / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D017469:Receptors, Fibronectin; D011994:Recombinant Proteins; C078592:amyloid beta-protein (1-40)