| Insights into Caspase-Mediated Apoptotic Pathways Induced by Amyloid-β in Cerebral Microvascular Endothelial Cells. | |
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MedLine Citation:
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PMID: 22156599 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background: The vascular deposition of amyloid known as cerebral amyloid angiopathy (CAA) - an age-associated condition and a common finding in Alzheimer's disease - compromises cerebral blood flow, causing macro/microhemorrhages and/or cognitive impairment. Very little is known about the mechanisms causing CAA-related degeneration of cerebral vascular cells. The Dutch E22Q familial amyloid-β (Aβ) variant is primarily associated with CAA, and manifests clinically with severe cerebral hemorrhages. Objective: We aimed to determine the molecular mechanisms causing apoptosis of cerebral endothelial cells in the presence of wild-type Aβ40 or its vasculotropic E22Q variant. Methods: We challenged human brain microvascular endothelial cells with both Aβ variants, and studied the apoptotic pathways triggered by these peptides. Results: Caspase-mediated apoptotic pathways were elicited by both peptides within time frames correlating with their aggregation properties and formation of oligomeric/protofibrillar assemblies. Our data revealed a primary activation of caspase-8 (typically triggered by death receptors) with secondary engagement of caspase-9, with cytochrome C and apoptosis-inducing factor release from the mitochondria, suggesting the independent or synergistic engagement of extrinsic and intrinsic apoptotic mechanisms. Conclusion: Our data demonstrate the induction of caspase-8- and caspase-9-dependent mitochondrial-mediated apoptotic pathways by Aβ oligomers/protofibrils in vascular cells, likely implicating a primary activation of death receptors. |
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Authors:
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Silvia Fossati; Jorge Ghiso; Agueda Rostagno |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-07 |
Journal Detail:
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Title: Neuro-degenerative diseases Volume: - ISSN: 1660-2862 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101189034 Medline TA: Neurodegener Dis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 S. Karger AG, Basel. |
Affiliation:
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Department of Pathology, New York University School of Medicine, New York, N.Y., USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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