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Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges

Immunization against amyloid-β (Aβ) peptides deposited in Alzheimer’s disease (AD) has shown considerable therapeutic effect in animal models however, the translation into human Alzheimer’s patients is challenging. In recent years, a number of promising Aβ immunotherapy trials failed to reach primar...

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Detalles Bibliográficos
Autores principales: Cynis, Holger, Frost, Jeffrey L., Crehan, Helen, Lemere, Cynthia A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929720/
https://www.ncbi.nlm.nih.gov/pubmed/27363697
http://dx.doi.org/10.1186/s13024-016-0115-2
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author Cynis, Holger
Frost, Jeffrey L.
Crehan, Helen
Lemere, Cynthia A.
author_facet Cynis, Holger
Frost, Jeffrey L.
Crehan, Helen
Lemere, Cynthia A.
author_sort Cynis, Holger
collection PubMed
description Immunization against amyloid-β (Aβ) peptides deposited in Alzheimer’s disease (AD) has shown considerable therapeutic effect in animal models however, the translation into human Alzheimer’s patients is challenging. In recent years, a number of promising Aβ immunotherapy trials failed to reach primary study endpoints. Aside from uncertainties in the selection of patients and the start and duration of treatment, these results also suggest that the mechanisms underlying AD are still not fully understood. Thorough characterizations of protein aggregates in AD brain have revealed a conspicuous heterogeneity of Aβ peptides enabling the study of the toxic potential of each of the major forms. One such form, amino-terminally truncated and modified pyroglutamate (pGlu)-3 Aβ peptide appears to play a seminal role for disease initiation, qualifying it as novel target for immunotherapy approaches.
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spelling pubmed-49297202016-07-02 Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges Cynis, Holger Frost, Jeffrey L. Crehan, Helen Lemere, Cynthia A. Mol Neurodegener Review Immunization against amyloid-β (Aβ) peptides deposited in Alzheimer’s disease (AD) has shown considerable therapeutic effect in animal models however, the translation into human Alzheimer’s patients is challenging. In recent years, a number of promising Aβ immunotherapy trials failed to reach primary study endpoints. Aside from uncertainties in the selection of patients and the start and duration of treatment, these results also suggest that the mechanisms underlying AD are still not fully understood. Thorough characterizations of protein aggregates in AD brain have revealed a conspicuous heterogeneity of Aβ peptides enabling the study of the toxic potential of each of the major forms. One such form, amino-terminally truncated and modified pyroglutamate (pGlu)-3 Aβ peptide appears to play a seminal role for disease initiation, qualifying it as novel target for immunotherapy approaches. BioMed Central 2016-06-30 /pmc/articles/PMC4929720/ /pubmed/27363697 http://dx.doi.org/10.1186/s13024-016-0115-2 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Review
Cynis, Holger
Frost, Jeffrey L.
Crehan, Helen
Lemere, Cynthia A.
Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges
title Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges
title_full Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges
title_fullStr Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges
title_full_unstemmed Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges
title_short Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges
title_sort immunotherapy targeting pyroglutamate-3 aβ: prospects and challenges
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929720/
https://www.ncbi.nlm.nih.gov/pubmed/27363697
http://dx.doi.org/10.1186/s13024-016-0115-2
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