| Endocannabinoids prevent β-amyloid-mediated lysosomal destabilization in cultured neurons. | |
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MedLine Citation:
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PMID: 20923768 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neuronal cell loss underlies the pathological decline in cognition and memory associated with Alzheimer disease (AD). Recently, targeting the endocannabinoid system in AD has emerged as a promising new approach to treatment. Studies have identified neuroprotective roles for endocannabinoids against key pathological events in the AD brain, including cell death by apoptosis. Elucidation of the apoptotic pathway evoked by β-amyloid (Aβ) is thus important for the development of therapeutic strategies that can thwart Aβ toxicity and preserve cell viability. We have previously reported that lysosomal membrane permeabilization plays a distinct role in the apoptotic pathway initiated by Aβ. In the present study, we provide evidence that the endocannabinoid system can stabilize lysosomes against Aβ-induced permeabilization and in turn sustain cell survival. We report that endocannabinoids stabilize lysosomes by preventing the Aβ-induced up-regulation of the tumor suppressor protein, p53, and its interaction with the lysosomal membrane. We also provide evidence that intracellular cannabinoid type 1 receptors play a role in stabilizing lysosomes against Aβ toxicity and thus highlight the functionality of these receptors. Given the deleterious effect of lysosomal membrane permeabilization on cell viability, stabilization of lysosomes with endocannabinoids may represent a novel mechanism by which these lipid modulators confer neuroprotection. |
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Authors:
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Janis Noonan; Riffat Tanveer; Allan Klompas; Aoife Gowran; Joanne McKiernan; Veronica A Campbell |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-05 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-29 Completed Date: 2010-12-30 Revised Date: 2012-01-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 38543-54 Citation Subset: IM |
Affiliation:
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Department of Physiology, School of Medicine and Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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drug therapy,
metabolism*,
pathology Amyloid beta-Peptides / metabolism* Animals Apoptosis Cell Survival Cells, Cultured Endocannabinoids / metabolism*, pharmacology Intracellular Membranes / metabolism*, pathology Lysosomes / metabolism*, pathology Male Neurons / metabolism*, pathology Permeability Rats Rats, Wistar Receptors, Cannabinoid Tumor Suppressor Protein p53 / metabolism Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Peptides; 0/Endocannabinoids; 0/Receptors, Cannabinoid; 0/Tumor Suppressor Protein p53 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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