| Selective inhibition of the membrane attack complex of complement by low molecular weight components of the aurin tricarboxylic acid synthetic complex. | |
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MedLine Citation:
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PMID: 22217416 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Complement plays a vital role in both the innate and adaptive immune systems. It recognizes a target, opsonizes it, generates anaphylatoxins, and directly kills cells through the membrane attack complex (MAC). This final function, which assembles C5b-9(n) on viable cell surfaces, can kill host cells through bystander lysis. Here we identify for the first time compounds that can inhibit bystander lysis while not interfering with the other essential functions of complement. We show that aurin tricarboxylic acid (ATA), aurin quadracarboxylic acid (AQA), and aurin hexacarboxylic acid (AHA), block the addition of C9 to C5b-8 so that the MAC cannot form. These molecules inhibit hemolysis of human, rat, and mouse red cells with a half maximal inhibitory concentration (IC(50)) in the nanomolar range. When given orally to Alzheimer disease type B6SJL-Tg mice, they inhibit MAC formation in serum and improve memory retention. On autopsy, they show no evidence of harm to any organ. Aurin tricarboxylic acid, aurin quadracarboxylic acid, and aurin hexacarboxylic acid may be effective therapeutic agents in Alzheimer disease and other degenerative disorders where self damage from the MAC occurs. |
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Authors:
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Moonhee Lee; Jian-Ping Guo; Claudia Schwab; Edith G McGeer; Patrick L McGeer |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-2 |
Journal Detail:
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Title: Neurobiology of aging Volume: - ISSN: 1558-1497 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8100437 Medline TA: Neurobiol Aging Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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