Aggregation and catabolism of disease-associated intra-Aβ mutations: reduced proteolysis of AβA21G by neprilysin
Five point mutations within the amyloid β-protein (Aβ) sequence of the APP gene are associated with hereditary diseases which are similar or identical to Alzheimer’s disease and encode: the A21G (Flemish), E22G (Arctic), E22K (Italian), E22Q (Dutch) and the D23N (Iowa) amino acid substitutions. Alth...
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ftpubmed:oai:pubmedcentral.nih.gov:3160758 2023-05-15T15:01:14+02:00 Aggregation and catabolism of disease-associated intra-Aβ mutations: reduced proteolysis of AβA21G by neprilysin Betts, Vicki Leissring, Malcolm A. Dolios, Georgia Wang, Rong Selkoe, Dennis J. Walsh, Dominic M. 2008-06-17 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160758 http://www.ncbi.nlm.nih.gov/pubmed/18602473 https://doi.org/10.1016/j.nbd.2008.06.001 en eng http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160758 http://www.ncbi.nlm.nih.gov/pubmed/18602473 http://dx.doi.org/10.1016/j.nbd.2008.06.001 © 2008 Elsevier Inc. All rights reserved. Article Text 2008 ftpubmed https://doi.org/10.1016/j.nbd.2008.06.001 2013-09-03T18:57:31Z Five point mutations within the amyloid β-protein (Aβ) sequence of the APP gene are associated with hereditary diseases which are similar or identical to Alzheimer’s disease and encode: the A21G (Flemish), E22G (Arctic), E22K (Italian), E22Q (Dutch) and the D23N (Iowa) amino acid substitutions. Although a substantial body of data exists on the effects of these mutations on Aβ production, whether or not intra-Aβ mutations alter degradation and how this relates to their aggregation state remain unclear. Here we report that the E22G, E22Q and the D23N substitutions significantly increase fibril nucleation and extension, whereas the E22K substitution exhibits only an increased rate of extension and the A21G substitution actually causes a decrease in the extension rate. Text Arctic PubMed Central (PMC) Arctic Neurobiology of Disease 31 3 442 450 |
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Article Betts, Vicki Leissring, Malcolm A. Dolios, Georgia Wang, Rong Selkoe, Dennis J. Walsh, Dominic M. Aggregation and catabolism of disease-associated intra-Aβ mutations: reduced proteolysis of AβA21G by neprilysin |
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Five point mutations within the amyloid β-protein (Aβ) sequence of the APP gene are associated with hereditary diseases which are similar or identical to Alzheimer’s disease and encode: the A21G (Flemish), E22G (Arctic), E22K (Italian), E22Q (Dutch) and the D23N (Iowa) amino acid substitutions. Although a substantial body of data exists on the effects of these mutations on Aβ production, whether or not intra-Aβ mutations alter degradation and how this relates to their aggregation state remain unclear. Here we report that the E22G, E22Q and the D23N substitutions significantly increase fibril nucleation and extension, whereas the E22K substitution exhibits only an increased rate of extension and the A21G substitution actually causes a decrease in the extension rate. |
format |
Text |
author |
Betts, Vicki Leissring, Malcolm A. Dolios, Georgia Wang, Rong Selkoe, Dennis J. Walsh, Dominic M. |
author_facet |
Betts, Vicki Leissring, Malcolm A. Dolios, Georgia Wang, Rong Selkoe, Dennis J. Walsh, Dominic M. |
author_sort |
Betts, Vicki |
title |
Aggregation and catabolism of disease-associated intra-Aβ mutations: reduced proteolysis of AβA21G by neprilysin |
title_short |
Aggregation and catabolism of disease-associated intra-Aβ mutations: reduced proteolysis of AβA21G by neprilysin |
title_full |
Aggregation and catabolism of disease-associated intra-Aβ mutations: reduced proteolysis of AβA21G by neprilysin |
title_fullStr |
Aggregation and catabolism of disease-associated intra-Aβ mutations: reduced proteolysis of AβA21G by neprilysin |
title_full_unstemmed |
Aggregation and catabolism of disease-associated intra-Aβ mutations: reduced proteolysis of AβA21G by neprilysin |
title_sort |
aggregation and catabolism of disease-associated intra-aβ mutations: reduced proteolysis of aβa21g by neprilysin |
publishDate |
2008 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160758 http://www.ncbi.nlm.nih.gov/pubmed/18602473 https://doi.org/10.1016/j.nbd.2008.06.001 |
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Arctic |
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Arctic |
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Arctic |
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Arctic |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160758 http://www.ncbi.nlm.nih.gov/pubmed/18602473 http://dx.doi.org/10.1016/j.nbd.2008.06.001 |
op_rights |
© 2008 Elsevier Inc. All rights reserved. |
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https://doi.org/10.1016/j.nbd.2008.06.001 |
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Neurobiology of Disease |
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31 |
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3 |
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442 |
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450 |
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1766333264489873408 |