Evidence from a mouse model supports repurposing an anti-asthmatic drug, bambuterol, against Alzheimer’s disease by administration through an intranasal route
Abstract Bambuterol is a long-acting anti-asthmatic prodrug which releases terbutaline. Terbutaline is an agonist of the β2-adrenergic receptors which is formed by decarbamoylation of bambuterol by butyrylcholinesterase. Inhibition of the latter, as well as activation of β2-AR, are of interest for t...
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07599-7 |
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| author | Anne-Claire Groo Thomas Curel Aurélie Malzert-Fréon Line Séguy Ophélie Bento Sophie Corvaisier Thomas Culerier Romain Legrand Noëlle Callizot Alexandre Henriques Georgia Culley Sylvie Claeysen Christophe Rochais Patrick Dallemagne |
| author_facet | Anne-Claire Groo Thomas Curel Aurélie Malzert-Fréon Line Séguy Ophélie Bento Sophie Corvaisier Thomas Culerier Romain Legrand Noëlle Callizot Alexandre Henriques Georgia Culley Sylvie Claeysen Christophe Rochais Patrick Dallemagne |
| author_sort | Anne-Claire Groo |
| collection | DOAJ |
| description | Abstract Bambuterol is a long-acting anti-asthmatic prodrug which releases terbutaline. Terbutaline is an agonist of the β2-adrenergic receptors which is formed by decarbamoylation of bambuterol by butyrylcholinesterase. Inhibition of the latter, as well as activation of β2-AR, are of interest for the treatment of Alzheimer’s disease (AD). Combining these two activities, bambuterol could express a good clinical efficacy against AD. The present work firstly confirmed the capacity of bambuterol to display in cellulo neuroprotective activities, reduction of Tau hyperphosphorylation and preservation of synapses in rat hippocampal neuronal cultures intoxicated with Aβ peptides. Further, bambuterol, in the form of a liposomal gel, showed a good bioavailability in CNS after intranasal administration, which should reduce any side effects linked to peripheral terbutaline release. Indeed, even if the latter is more selective than other β2-mimetics towards bronchial β2-AR, cardiovascular effects (tachycardia, arrhythmias…) could occur upon cardiac β1-AR activation. Finally, intranasal administration of low doses of bambuterol gel in mice intoxicated with Aβ peptides, prevented long-term spatial memory impairment and showed beneficial effects on the survival of neurons and on synapse preservation. |
| format | Article |
| id | doaj-art-21d16ec2f95d46f0b229238b1a080f57 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-21d16ec2f95d46f0b229238b1a080f572025-02-02T12:37:26ZengNature PortfolioCommunications Biology2399-36422025-02-018111410.1038/s42003-025-07599-7Evidence from a mouse model supports repurposing an anti-asthmatic drug, bambuterol, against Alzheimer’s disease by administration through an intranasal routeAnne-Claire Groo0Thomas Curel1Aurélie Malzert-Fréon2Line Séguy3Ophélie Bento4Sophie Corvaisier5Thomas Culerier6Romain Legrand7Noëlle Callizot8Alexandre Henriques9Georgia Culley10Sylvie Claeysen11Christophe Rochais12Patrick Dallemagne13Université de Caen Normandie, CERMN UR4258, Normandie UnivIGF, Univ. Montpellier, CNRS, INSERMUniversité de Caen Normandie, CERMN UR4258, Normandie UnivUniversité de Caen Normandie, CERMN UR4258, Normandie UnivIGF, Univ. Montpellier, CNRS, INSERMUniversité de Caen Normandie, CERMN UR4258, Normandie UnivUniversité de Caen Normandie, CERMN UR4258, Normandie UnivRONOMA PharmaNeuro-SysNeuro-SysNeuro-SysIGF, Univ. Montpellier, CNRS, INSERMUniversité de Caen Normandie, CERMN UR4258, Normandie UnivUniversité de Caen Normandie, CERMN UR4258, Normandie UnivAbstract Bambuterol is a long-acting anti-asthmatic prodrug which releases terbutaline. Terbutaline is an agonist of the β2-adrenergic receptors which is formed by decarbamoylation of bambuterol by butyrylcholinesterase. Inhibition of the latter, as well as activation of β2-AR, are of interest for the treatment of Alzheimer’s disease (AD). Combining these two activities, bambuterol could express a good clinical efficacy against AD. The present work firstly confirmed the capacity of bambuterol to display in cellulo neuroprotective activities, reduction of Tau hyperphosphorylation and preservation of synapses in rat hippocampal neuronal cultures intoxicated with Aβ peptides. Further, bambuterol, in the form of a liposomal gel, showed a good bioavailability in CNS after intranasal administration, which should reduce any side effects linked to peripheral terbutaline release. Indeed, even if the latter is more selective than other β2-mimetics towards bronchial β2-AR, cardiovascular effects (tachycardia, arrhythmias…) could occur upon cardiac β1-AR activation. Finally, intranasal administration of low doses of bambuterol gel in mice intoxicated with Aβ peptides, prevented long-term spatial memory impairment and showed beneficial effects on the survival of neurons and on synapse preservation.https://doi.org/10.1038/s42003-025-07599-7 |
| spellingShingle | Anne-Claire Groo Thomas Curel Aurélie Malzert-Fréon Line Séguy Ophélie Bento Sophie Corvaisier Thomas Culerier Romain Legrand Noëlle Callizot Alexandre Henriques Georgia Culley Sylvie Claeysen Christophe Rochais Patrick Dallemagne Evidence from a mouse model supports repurposing an anti-asthmatic drug, bambuterol, against Alzheimer’s disease by administration through an intranasal route Communications Biology |
| title | Evidence from a mouse model supports repurposing an anti-asthmatic drug, bambuterol, against Alzheimer’s disease by administration through an intranasal route |
| title_full | Evidence from a mouse model supports repurposing an anti-asthmatic drug, bambuterol, against Alzheimer’s disease by administration through an intranasal route |
| title_fullStr | Evidence from a mouse model supports repurposing an anti-asthmatic drug, bambuterol, against Alzheimer’s disease by administration through an intranasal route |
| title_full_unstemmed | Evidence from a mouse model supports repurposing an anti-asthmatic drug, bambuterol, against Alzheimer’s disease by administration through an intranasal route |
| title_short | Evidence from a mouse model supports repurposing an anti-asthmatic drug, bambuterol, against Alzheimer’s disease by administration through an intranasal route |
| title_sort | evidence from a mouse model supports repurposing an anti asthmatic drug bambuterol against alzheimer s disease by administration through an intranasal route |
| url | https://doi.org/10.1038/s42003-025-07599-7 |
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