Histidines 13 and 14 in the Aβ sequence are targets for inhibition of Alzheimer's disease Aβ ion channel and cytotoxicity
The fact that Alzheimer's beta amyloid (Aβ) peptides forms cation channels in lipid bilayers was discovered during the course of our experiments in the laboratory of "Guayo" Rojas at NIH in Bethesda, Maryland (USA). Recently, we found that the Aβ ion channel could be...
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Sociedad de Biología de Chile
2006
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oai:scielo:S0716-976020060003000072014-01-24Histidines 13 and 14 in the Aβ sequence are targets for inhibition of Alzheimer's disease Aβ ion channel and cytotoxicityDÍAZ,JUAN CARLOSLINNEHAN,JOHNPOLLARD,HARVEYARISPE,NELSON Alzheimer's disease beta amyloid ion channel blockers peptides histidine toxicity The fact that Alzheimer's beta amyloid (Aβ) peptides forms cation channels in lipid bilayers was discovered during the course of our experiments in the laboratory of "Guayo" Rojas at NIH in Bethesda, Maryland (USA). Recently, we found that the Aβ ion channel could be blocked selectively with small peptides that copy the amino acid sequence of the predicted mouth region of the Aβ channel pore. We now have searched for the essential amino acid residues required for this blocking effect by mutations. We found that the ability of peptides to block Aβ channel activity could be lost by replacement of histidines 13 and 14 by alanine or lysine. The amino acid substitution also resulted in the loss of the capacity of the peptides to protect cells from Aβ cytotoxicity. These data thus contribute to the definition of the region of the Aβ sequence that participates in the formation of the channel pore. Additionally, these data support the hypothesis that the ion channel activity of Ab contributes significantly to the cytotoxic properties of Aβ. These data also emphasize the potential value in using inhibition of Aβ ion channel activity as an end point for Alzheimer's disease drug discovery.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.39 n.3 20062006-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000300007en10.4067/S0716-97602006000300007 |
| institution |
Scielo Chile |
| collection |
Scielo Chile |
| language |
English |
| topic |
Alzheimer's disease beta amyloid ion channel blockers peptides histidine toxicity |
| spellingShingle |
Alzheimer's disease beta amyloid ion channel blockers peptides histidine toxicity DÍAZ,JUAN CARLOS LINNEHAN,JOHN POLLARD,HARVEY ARISPE,NELSON Histidines 13 and 14 in the Aβ sequence are targets for inhibition of Alzheimer's disease Aβ ion channel and cytotoxicity |
| description |
The fact that Alzheimer's beta amyloid (Aβ) peptides forms cation channels in lipid bilayers was discovered during the course of our experiments in the laboratory of "Guayo" Rojas at NIH in Bethesda, Maryland (USA). Recently, we found that the Aβ ion channel could be blocked selectively with small peptides that copy the amino acid sequence of the predicted mouth region of the Aβ channel pore. We now have searched for the essential amino acid residues required for this blocking effect by mutations. We found that the ability of peptides to block Aβ channel activity could be lost by replacement of histidines 13 and 14 by alanine or lysine. The amino acid substitution also resulted in the loss of the capacity of the peptides to protect cells from Aβ cytotoxicity. These data thus contribute to the definition of the region of the Aβ sequence that participates in the formation of the channel pore. Additionally, these data support the hypothesis that the ion channel activity of Ab contributes significantly to the cytotoxic properties of Aβ. These data also emphasize the potential value in using inhibition of Aβ ion channel activity as an end point for Alzheimer's disease drug discovery. |
| author |
DÍAZ,JUAN CARLOS LINNEHAN,JOHN POLLARD,HARVEY ARISPE,NELSON |
| author_facet |
DÍAZ,JUAN CARLOS LINNEHAN,JOHN POLLARD,HARVEY ARISPE,NELSON |
| author_sort |
DÍAZ,JUAN CARLOS |
| title |
Histidines 13 and 14 in the Aβ sequence are targets for inhibition of Alzheimer's disease Aβ ion channel and cytotoxicity |
| title_short |
Histidines 13 and 14 in the Aβ sequence are targets for inhibition of Alzheimer's disease Aβ ion channel and cytotoxicity |
| title_full |
Histidines 13 and 14 in the Aβ sequence are targets for inhibition of Alzheimer's disease Aβ ion channel and cytotoxicity |
| title_fullStr |
Histidines 13 and 14 in the Aβ sequence are targets for inhibition of Alzheimer's disease Aβ ion channel and cytotoxicity |
| title_full_unstemmed |
Histidines 13 and 14 in the Aβ sequence are targets for inhibition of Alzheimer's disease Aβ ion channel and cytotoxicity |
| title_sort |
histidines 13 and 14 in the aβ sequence are targets for inhibition of alzheimer's disease aβ ion channel and cytotoxicity |
| publisher |
Sociedad de Biología de Chile |
| publishDate |
2006 |
| url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000300007 |
| work_keys_str_mv |
AT diazjuancarlos histidines13and14inthea946sequencearetargetsforinhibitionofalzheimersdiseasea946ionchannelandcytotoxicity AT linnehanjohn histidines13and14inthea946sequencearetargetsforinhibitionofalzheimersdiseasea946ionchannelandcytotoxicity AT pollardharvey histidines13and14inthea946sequencearetargetsforinhibitionofalzheimersdiseasea946ionchannelandcytotoxicity AT arispenelson histidines13and14inthea946sequencearetargetsforinhibitionofalzheimersdiseasea946ionchannelandcytotoxicity |
| _version_ |
1718441405266788352 |