Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amyloid beta-Protein Precursor / administration & dosage
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Amyloid beta-Protein Precursor / metabolism
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Amyloid beta-Protein Precursor / pharmacology*
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Animals
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Brain / drug effects
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Brain / pathology*
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Cell Line
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Cerebral Ventricles / drug effects
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Cerebral Ventricles / physiology
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Hippocampus / drug effects
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Hippocampus / pathology
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Humans
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Injections, Intraventricular
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Ischemic Attack, Transient / pathology*
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Ischemic Attack, Transient / prevention & control*
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Kidney
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Male
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Neurons / drug effects
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Neurons / pathology*
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Pyramidal Cells / drug effects
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Pyramidal Cells / pathology
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Rats
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Rats, Wistar
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / pharmacology
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Serum Albumin, Bovine / administration & dosage
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Serum Albumin, Bovine / pharmacology
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Stereotaxic Techniques
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Transfection
Substances
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Amyloid beta-Protein Precursor
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Recombinant Proteins
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Serum Albumin, Bovine