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Repurposing drugs against Alzheimer’s disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD?
Therapeutic approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models and in humans suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when trea...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Vienna
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374694/ https://www.ncbi.nlm.nih.gov/pubmed/37014414 http://dx.doi.org/10.1007/s00702-023-02618-5 |
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author | Leßmann, Volkmar Kartalou, Georgia-Ioanna Endres, Thomas Pawlitzki, Marc Gottmann, Kurt |
author_facet | Leßmann, Volkmar Kartalou, Georgia-Ioanna Endres, Thomas Pawlitzki, Marc Gottmann, Kurt |
author_sort | Leßmann, Volkmar |
collection | PubMed |
description | Therapeutic approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models and in humans suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals or in elderly humans before onset of disease symptoms. However, a pharmacological treatment that can reverse memory deficits in AD patients was thus far not identified. Importantly, AD disease-related dysfunctions have increasingly been associated with neuro-inflammatory mechanisms and searching for anti-inflammatory medication to treat AD seems promising. Like for other diseases, repurposing of FDA-approved drugs for treatment of AD is an ideally suited strategy to reduce the time to bring such medication into clinical practice. Of note, the sphingosine-1-phosphate analogue fingolimod (FTY720) was FDA-approved in 2010 for treatment of multiple sclerosis patients. It binds to the five different isoforms of Sphingosine-1-phosphate receptors (S1PRs) that are widely distributed across human organs. Interestingly, recent studies in five different mouse models of AD suggest that FTY720 treatment, even when starting after onset of AD symptoms, can reverse synaptic deficits and memory dysfunction in these AD mouse models. Furthermore, a very recent multi-omics study identified mutations in the sphingosine/ceramide pathway as a risk factor for sporadic AD, suggesting S1PRs as promising drug target in AD patients. Therefore, progressing with FDA-approved S1PR modulators into human clinical trials might pave the way for these potential disease modifying anti-AD drugs. |
format | Online Article Text |
id | pubmed-10374694 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Vienna |
record_format | MEDLINE/PubMed |
spelling | pubmed-103746942023-07-29 Repurposing drugs against Alzheimer’s disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD? Leßmann, Volkmar Kartalou, Georgia-Ioanna Endres, Thomas Pawlitzki, Marc Gottmann, Kurt J Neural Transm (Vienna) Neurology and Preclinical Neurological Studies - Review Article Therapeutic approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models and in humans suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals or in elderly humans before onset of disease symptoms. However, a pharmacological treatment that can reverse memory deficits in AD patients was thus far not identified. Importantly, AD disease-related dysfunctions have increasingly been associated with neuro-inflammatory mechanisms and searching for anti-inflammatory medication to treat AD seems promising. Like for other diseases, repurposing of FDA-approved drugs for treatment of AD is an ideally suited strategy to reduce the time to bring such medication into clinical practice. Of note, the sphingosine-1-phosphate analogue fingolimod (FTY720) was FDA-approved in 2010 for treatment of multiple sclerosis patients. It binds to the five different isoforms of Sphingosine-1-phosphate receptors (S1PRs) that are widely distributed across human organs. Interestingly, recent studies in five different mouse models of AD suggest that FTY720 treatment, even when starting after onset of AD symptoms, can reverse synaptic deficits and memory dysfunction in these AD mouse models. Furthermore, a very recent multi-omics study identified mutations in the sphingosine/ceramide pathway as a risk factor for sporadic AD, suggesting S1PRs as promising drug target in AD patients. Therefore, progressing with FDA-approved S1PR modulators into human clinical trials might pave the way for these potential disease modifying anti-AD drugs. Springer Vienna 2023-04-04 2023 /pmc/articles/PMC10374694/ /pubmed/37014414 http://dx.doi.org/10.1007/s00702-023-02618-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Neurology and Preclinical Neurological Studies - Review Article Leßmann, Volkmar Kartalou, Georgia-Ioanna Endres, Thomas Pawlitzki, Marc Gottmann, Kurt Repurposing drugs against Alzheimer’s disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD? |
title | Repurposing drugs against Alzheimer’s disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD? |
title_full | Repurposing drugs against Alzheimer’s disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD? |
title_fullStr | Repurposing drugs against Alzheimer’s disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD? |
title_full_unstemmed | Repurposing drugs against Alzheimer’s disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD? |
title_short | Repurposing drugs against Alzheimer’s disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD? |
title_sort | repurposing drugs against alzheimer’s disease: can the anti-multiple sclerosis drug fingolimod (fty720) effectively tackle inflammation processes in ad? |
topic | Neurology and Preclinical Neurological Studies - Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374694/ https://www.ncbi.nlm.nih.gov/pubmed/37014414 http://dx.doi.org/10.1007/s00702-023-02618-5 |
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