| Carboxyfullerenes as neuroprotective agents. | |
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MedLine Citation:
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PMID: 9256500 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Two regioisomers with C3 or D3 symmetry of water-soluble carboxylic acid C60 derivatives, containing three malonic acid groups per molecule, were synthesized and found to be equipotent free radical scavengers in solution as assessed by EPR analysis. Both compounds also inhibited the excitotoxic death of cultured cortical neurons induced by exposure to N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or oxygen-glucose deprivation, but the C3 regioisomer was more effective than the D3 regioisomer, possibly reflecting its polar nature and attendant greater ability to enter lipid membranes. At 100 microM, the C3 derivative fully blocked even rapidly triggered, NMDA receptor-mediated toxicity, a form of toxicity with limited sensitivity to all other classes of free radical scavengers we have tested. The C3 derivative also reduced apoptotic neuronal death induced by either serum deprivation or exposure to Abeta1-42 protein. Furthermore, continuous infusion of the C3 derivative in a transgenic mouse carrying the human mutant (G93A) superoxide dismutase gene responsible for a form of familial amyotrophic lateral sclerosis, delayed both death and functional deterioration. These data suggest that polar carboxylic acid C60 derivatives may have attractive therapeutic properties in several acute or chronic neurodegenerative diseases. |
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Authors:
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L L Dugan; D M Turetsky; C Du; D Lobner; M Wheeler; C R Almli; C K Shen; T Y Luh; D W Choi; T S Lin |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 94 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 1997 Aug |
Date Detail:
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Created Date: 1997-09-17 Completed Date: 1997-09-17 Revised Date: 2013-04-17 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 9434-9 Citation Subset: IM |
Affiliation:
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Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain / drug effects* Carboxylic Acids / chemistry*, pharmacology* Cell Membrane / drug effects* Free Radicals Humans Mice Neuroprotective Agents / chemistry*, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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NS 30337/NS/NINDS NIH HHS; NS 31248/NS/NINDS NIH HHS; NS 32636/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carboxylic Acids; 0/Free Radicals; 0/Neuroprotective Agents |
| Comments/Corrections | |
Erratum In:
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Proc Natl Acad Sci U S A 1997 Oct 28;94(22):12241 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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