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Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease

Recent clinical data with three therapeutic anti-Aβ antibodies have demonstrated that removal of Aβ-amyloid plaques in early Alzheimer's disease (AD) can attenuate disease progression. This ground-breaking progress in AD medicine has validated both the amyloid cascade hypothesis and Aβ-amyloid...

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Autores principales: Nordvall, Gunnar, Lundkvist, Johan, Sandin, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613654/
https://www.ncbi.nlm.nih.gov/pubmed/37908487
http://dx.doi.org/10.3389/fnmol.2023.1279740
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author Nordvall, Gunnar
Lundkvist, Johan
Sandin, Johan
author_facet Nordvall, Gunnar
Lundkvist, Johan
Sandin, Johan
author_sort Nordvall, Gunnar
collection PubMed
description Recent clinical data with three therapeutic anti-Aβ antibodies have demonstrated that removal of Aβ-amyloid plaques in early Alzheimer's disease (AD) can attenuate disease progression. This ground-breaking progress in AD medicine has validated both the amyloid cascade hypothesis and Aβ-amyloid as therapeutic targets. These results also strongly support therapeutic approaches that aim to reduce the production of amyloidogenic Aβ to prevent the formation of Aβ-pathology. One such strategy, so-called gamma-secretase modulators (GSM), has been thoroughly explored in preclinical settings but has yet to be fully tested in clinical trials. Recent scientific progress has shed new light on the role of Aβ in Alzheimer's disease and suggests that GSMs exhibit specific pharmacological features that hold great promise for the prevention and treatment of Alzheimer's disease. In this short review, we discuss the data that support why it is important to continue to progress in this class of compounds.
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spelling pubmed-106136542023-10-31 Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease Nordvall, Gunnar Lundkvist, Johan Sandin, Johan Front Mol Neurosci Molecular Neuroscience Recent clinical data with three therapeutic anti-Aβ antibodies have demonstrated that removal of Aβ-amyloid plaques in early Alzheimer's disease (AD) can attenuate disease progression. This ground-breaking progress in AD medicine has validated both the amyloid cascade hypothesis and Aβ-amyloid as therapeutic targets. These results also strongly support therapeutic approaches that aim to reduce the production of amyloidogenic Aβ to prevent the formation of Aβ-pathology. One such strategy, so-called gamma-secretase modulators (GSM), has been thoroughly explored in preclinical settings but has yet to be fully tested in clinical trials. Recent scientific progress has shed new light on the role of Aβ in Alzheimer's disease and suggests that GSMs exhibit specific pharmacological features that hold great promise for the prevention and treatment of Alzheimer's disease. In this short review, we discuss the data that support why it is important to continue to progress in this class of compounds. Frontiers Media S.A. 2023-10-16 /pmc/articles/PMC10613654/ /pubmed/37908487 http://dx.doi.org/10.3389/fnmol.2023.1279740 Text en Copyright © 2023 Nordvall, Lundkvist and Sandin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Neuroscience
Nordvall, Gunnar
Lundkvist, Johan
Sandin, Johan
Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease
title Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease
title_full Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease
title_fullStr Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease
title_full_unstemmed Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease
title_short Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease
title_sort gamma-secretase modulators: a promising route for the treatment of alzheimer's disease
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613654/
https://www.ncbi.nlm.nih.gov/pubmed/37908487
http://dx.doi.org/10.3389/fnmol.2023.1279740
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