Secreted forms of beta-amyloid precursor protein protect against ischemic brain injury.
The beta-amyloid precursor protein (beta APP) is the source of the amyloid beta-peptide that accumulates in the brain in Alzheimer's disease. A major processing pathway for beta APP involves an enzymatic cleavage within the amyloid beta-peptide sequence that liberates secreted forms of beta APP (APPss) into the extracellular milieu. We now report that postischemic administration of these APPss intracerebroventricularly protects neurons in the CA1 region of rat hippocampus against ischemic injury. Treatment with APPs695 or APPs751 resulted in increased neuronal survival, and the surviving cells were functional as demonstrated by their ability to synthesize protein. These data provide direct evidence for a neuroprotective action of APPss in vivo.
Department of Anatomy, University of Kentucky.
V L
VL
Smith-Swintosky
L C
LC
Pettigrew
S D
SD
Craddock
A R
AR
Culwell
R E
RE
Rydel
M P
MP
Mattson
D016564:Amyloid beta-Protein Precursor / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002460:Cell Line; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000517:prevention & control*; D007668:Kidney; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000494:pharmacology; D013238:Stereotaxic Techniques; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D011994:Recombinant Proteins; D012710:Serum Albumin, Bovine