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| Title: | Copper complexing decreases the ability of amyloid beta peptide to cross the BBB and enter brain parenchyma |
| Author (s): | Mare, S. Penugonda, S.. Robinson, S. Dohgu, S. Banks, W.A. Ercal, Nuran |
| Department/Lab Affiliations: | Center for Environmental Science and Technology (CEST) Chemistry Environmental Research Center |
| Keywords: | Alzheimer's disease Amyloid beta peptide Copper |
| Issue Date: | 2007 |
| Publisher: | Elsevier |
| Citation: | Mare, S Penugonda, SM. Robinson, S. Dohgu, WA Banks, and N. Ercal, Copper complexing decreases the ability of amyloid beta peptide to cross the BBB and enter brain parenchyma, Peptides, Vol. 28, 2007, pp. 1424-1432, 2007. |
| Abstract: | The amyloid hypothesis states that amyloid beta protein (Aβ) plays a major causal role in the onset of Alzheimer's disease. Toxicity of Aβ can be modified by metal ions. Two mechanisms by which such Aβ and metal ions could interact are by enhanced oxidative stress or by altered fibrillation. Specifically, Aβ fibrillation is increased by aluminum (Al) and copper (Cu) and Al also increases Aβ uptake into brain. Here, we determined whether chelation with Cu would alter uptake of the human or rat 1-42 form of Aβ (Aβ42) by brain or alter Aβ-induced oxidative stress in an immortalized line of rat brain endothelial cells (RBE4). We found that Cu enhanced cytotoxicity of rat, but not of human Aβ, had no effect on glutathione (GSH) or cysteine (CYS) levels. Cu significantly decreased homocysteine (HCYS) levels when complexed with Aβ. Cu chelation did not alter Aβ uptake into brain or other tissues (except for kidney) or alter clearance from blood or brain in vivo, but did increase efflux in an in vitro model of the blood–brain barrier (BBB). Chelation to Cu also impaired the capillary to brain transport of Aβ, an effect opposite to that previously found for chelation of Aβ to Al. These results show that metal ions have varied effects on Aβ uptake by brain and that Cu could be protective against the neurotoxic effects of circulating Aβ. |
| Type: | Article - Journal text |
| Copyright Notice: | Pre-print: author can archive with restrictions;Restriction: This does not include Cell Press; Post-print: author can archive; This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder. FULL COPYRIGHT INFORMATION: |
| Publisher URL: | |
| Link to this page: |
| title | Copper complexing decreases the ability of amyloid beta peptide to cross the BBB and enter brain parenchyma |
| contributor.author | Mare, S. |
| contributor.author | Penugonda, S.. |
| contributor.author | Robinson, S. |
| contributor.author | Dohgu, S. |
| contributor.author | Banks, W.A. |
| contributor.author | Ercal, Nuran |
| contributor.deptlab | Center for Environmental Science and Technology (CEST) |
| contributor.deptlab | Chemistry |
| contributor.deptlab | Environmental Research Center |
| subject | Alzheimer's disease |
| subject | Amyloid beta peptide |
| subject | Copper |
| date.issued | 2007 |
| publisher | Elsevier |
| identifier.citation | Mare, S Penugonda, SM. Robinson, S. Dohgu, WA Banks, and N. Ercal, Copper complexing decreases the ability of amyloid beta peptide to cross the BBB and enter brain parenchyma, Peptides, Vol. 28, 2007, pp. 1424-1432, 2007. |
| identifier.pub.URI | |
| description.abstract | The amyloid hypothesis states that amyloid beta protein (Aβ) plays a major causal role in the onset of Alzheimer's disease. Toxicity of Aβ can be modified by metal ions. Two mechanisms by which such Aβ and metal ions could interact are by enhanced oxidative stress or by altered fibrillation. Specifically, Aβ fibrillation is increased by aluminum (Al) and copper (Cu) and Al also increases Aβ uptake into brain. Here, we determined whether chelation with Cu would alter uptake of the human or rat 1-42 form of Aβ (Aβ42) by brain or alter Aβ-induced oxidative stress in an immortalized line of rat brain endothelial cells (RBE4). We found that Cu enhanced cytotoxicity of rat, but not of human Aβ, had no effect on glutathione (GSH) or cysteine (CYS) levels. Cu significantly decreased homocysteine (HCYS) levels when complexed with Aβ. Cu chelation did not alter Aβ uptake into brain or other tissues (except for kidney) or alter clearance from blood or brain in vivo, but did increase efflux in an in vitro model of the blood–brain barrier (BBB). Chelation to Cu also impaired the capillary to brain transport of Aβ, an effect opposite to that previously found for chelation of Aβ to Al. These results show that metal ions have varied effects on Aβ uptake by brain and that Cu could be protective against the neurotoxic effects of circulating Aβ. |
| type | Article - Journal |
| type.DCMIType | text |
| type.status | Postprint |
| rights | Pre-print: author can archive with restrictions;Restriction: This does not include Cell Press; Post-print: author can archive; |
| rights | This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder. |
| rights.URI | |
| date.available | 2008-06-13T14:18:41Z |
| identifier.persist.URI |