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Blood brain barrier endothelial cells express candidate amyloid precursor protein-cleaving secretases.
- Source :
-
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis [Amyloid] 1998 Sep; Vol. 5 (3), pp. 153-62. - Publication Year :
- 1998
-
Abstract
- Proteolytic cleavage of the amyloid precursor protein (A beta PP) results in the generation of the amyloidogenic fragment known as amyloid beta peptide (A beta). Deposition of A beta in the brain parenchyma and cerebrovasculature is a feature of Alzheimer's disease (AD). To date, the process whereby A beta is generated and deposited remains unclear. We have previously established that activated platelets from AD patients retain more A beta PP on their surface than control platelets. We report here that an endothelial cell-derived enzyme can cleave this surface platelet A beta PP. Human blood brain barrier endothelial cells from brains of AD patients were assayed for potential A beta PP-cleaving enzymes using synthetic peptide substrates encompassing the A beta N-terminus cleavage site. A protease activity capable of cleaving A beta PP on the surface of AD platelets was noted. The A beta PP cleavage is partially inhibited by EDTA, by ZincOV, as well as by a specific inhibitor of the Zn metalloprotease E.C.3.4.24.15. Furthermore, the protease is recognized by an antibody directed against it, using immunohistochemistry, Western blot analysis and flow cytometry. The protease is not secreted, but rather resides intracellularly as well as on the surface of the endothelial cells. The data suggest that E.C.3.4.24.15 synthesized by brain endothelial cells may process the platelet-derived A beta PP, yielding fragments which could contribute to cerebrovascular A beta deposits.
- Subjects :
- Amyloid Precursor Protein Secretases
Antibody Specificity
Aspartic Acid Endopeptidases
Blood Platelets metabolism
Edetic Acid pharmacology
Endopeptidases immunology
Humans
Hydroxamic Acids pharmacology
Immunohistochemistry
Metalloendopeptidases antagonists & inhibitors
Metalloendopeptidases immunology
Oligopeptides metabolism
Alzheimer Disease enzymology
Amyloid beta-Protein Precursor metabolism
Blood-Brain Barrier
Endopeptidases isolation & purification
Endothelium, Vascular enzymology
Metalloendopeptidases isolation & purification
Subjects
Details
- Language :
- English
- ISSN :
- 1350-6129
- Volume :
- 5
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
- Publication Type :
- Academic Journal
- Accession number :
- 9818052
- Full Text :
- https://doi.org/10.3109/13506129809003841