A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential
Abstract Introduction The neuronal mechanism driving Alzheimer's disease (AD) is incompletely understood. Methods Immunohistochemistry, pharmacology, biochemistry, and behavioral testing are employed in two pathological contexts—AD and a transgenic mouse model—to investigate T14, a 14mer peptid...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/trc2.12274 |
| _version_ | 1797949031058505728 |
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| author | Susan A. Greenfield Gregory M. Cole Clive W. Coen Sally Frautschy Ram P. Singh Marisa Mekkittikul Sara Garcia‐Ratés Paul Morrill Owen Hollings Matt Passmore Sibah Hasan Nikisha Carty Silvia Bison Laura Piccoli Renzo Carletti Stephano Tacconi Anna Chalidou Matthew Pedercini Tim Kroecher Hubert Astner Philip A. Gerrard |
| author_facet | Susan A. Greenfield Gregory M. Cole Clive W. Coen Sally Frautschy Ram P. Singh Marisa Mekkittikul Sara Garcia‐Ratés Paul Morrill Owen Hollings Matt Passmore Sibah Hasan Nikisha Carty Silvia Bison Laura Piccoli Renzo Carletti Stephano Tacconi Anna Chalidou Matthew Pedercini Tim Kroecher Hubert Astner Philip A. Gerrard |
| author_sort | Susan A. Greenfield |
| collection | DOAJ |
| description | Abstract Introduction The neuronal mechanism driving Alzheimer's disease (AD) is incompletely understood. Methods Immunohistochemistry, pharmacology, biochemistry, and behavioral testing are employed in two pathological contexts—AD and a transgenic mouse model—to investigate T14, a 14mer peptide, as a key signaling molecule in the neuropathology. Results T14 increases in AD brains as the disease progresses and is conspicuous in 5XFAD mice, where its immunoreactivity corresponds to that seen in AD: neurons immunoreactive for T14 in proximity to T14‐immunoreactive plaques. NBP14 is a cyclized version of T14, which dose‐dependently displaces binding of its linear counterpart to alpha‐7 nicotinic receptors in AD brains. In 5XFAD mice, intranasal NBP14 for 14 weeks decreases brain amyloid and restores novel object recognition to that in wild‐types. Discussion These findings indicate that the T14 system, for which the signaling pathway is described here, contributes to the neuropathological process and that NBP14 warrants consideration for its therapeutic potential. |
| first_indexed | 2024-04-10T21:52:55Z |
| format | Article |
| id | doaj.art-07684a389acc417a9545fbf1b57c644f |
| institution | Directory Open Access Journal |
| issn | 2352-8737 |
| language | English |
| last_indexed | 2024-04-10T21:52:55Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj.art-07684a389acc417a9545fbf1b57c644f2023-01-18T11:41:03ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372022-01-0181n/an/a10.1002/trc2.12274A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potentialSusan A. Greenfield0Gregory M. Cole1Clive W. Coen2Sally Frautschy3Ram P. Singh4Marisa Mekkittikul5Sara Garcia‐Ratés6Paul Morrill7Owen Hollings8Matt Passmore9Sibah Hasan10Nikisha Carty11Silvia Bison12Laura Piccoli13Renzo Carletti14Stephano Tacconi15Anna Chalidou16Matthew Pedercini17Tim Kroecher18Hubert Astner19Philip A. Gerrard20Culham Science Centre Neuro‐Bio Ltd Abingdon UKDepartment of Neurology & Medicine USA and Veterans Affairs Healthcare System David Geffen School of Medicine at UCLA Los Angeles USAFaculty of Life Sciences & Medicine King's College London London UKDepartment of Neurology & Medicine USA and Veterans Affairs Healthcare System David Geffen School of Medicine at UCLA Los Angeles USADepartment of Neurology & Medicine USA and Veterans Affairs Healthcare System David Geffen School of Medicine at UCLA Los Angeles USADepartment of Neurology & Medicine USA and Veterans Affairs Healthcare System David Geffen School of Medicine at UCLA Los Angeles USACulham Science Centre Neuro‐Bio Ltd Abingdon UKCulham Science Centre Neuro‐Bio Ltd Abingdon UKCulham Science Centre Neuro‐Bio Ltd Abingdon UKCulham Science Centre Neuro‐Bio Ltd Abingdon UKCulham Science Centre Neuro‐Bio Ltd Abingdon UKManfred Eigen Campus Evotec SE Hamburg GermanyAptuit Evotec (Verona) Srl Verona ItalyAptuit Evotec (Verona) Srl Verona ItalyAptuit Evotec (Verona) Srl Verona ItalyAptuit Evotec (Verona) Srl Verona ItalyAptuit Evotec (Verona) Srl Verona ItalyAptuit Evotec (Verona) Srl Verona ItalyManfred Eigen Campus Evotec SE Hamburg GermanyAptuit Evotec (Verona) Srl Verona ItalyAptuit Evotec (Verona) Srl Verona ItalyAbstract Introduction The neuronal mechanism driving Alzheimer's disease (AD) is incompletely understood. Methods Immunohistochemistry, pharmacology, biochemistry, and behavioral testing are employed in two pathological contexts—AD and a transgenic mouse model—to investigate T14, a 14mer peptide, as a key signaling molecule in the neuropathology. Results T14 increases in AD brains as the disease progresses and is conspicuous in 5XFAD mice, where its immunoreactivity corresponds to that seen in AD: neurons immunoreactive for T14 in proximity to T14‐immunoreactive plaques. NBP14 is a cyclized version of T14, which dose‐dependently displaces binding of its linear counterpart to alpha‐7 nicotinic receptors in AD brains. In 5XFAD mice, intranasal NBP14 for 14 weeks decreases brain amyloid and restores novel object recognition to that in wild‐types. Discussion These findings indicate that the T14 system, for which the signaling pathway is described here, contributes to the neuropathological process and that NBP14 warrants consideration for its therapeutic potential.https://doi.org/10.1002/trc2.122745XFADacetylcholinesterasealphaLISAAlzheimer's diseaseamyloid betabasal forebrain |
| spellingShingle | Susan A. Greenfield Gregory M. Cole Clive W. Coen Sally Frautschy Ram P. Singh Marisa Mekkittikul Sara Garcia‐Ratés Paul Morrill Owen Hollings Matt Passmore Sibah Hasan Nikisha Carty Silvia Bison Laura Piccoli Renzo Carletti Stephano Tacconi Anna Chalidou Matthew Pedercini Tim Kroecher Hubert Astner Philip A. Gerrard A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential Alzheimer’s & Dementia: Translational Research & Clinical Interventions 5XFAD acetylcholinesterase alphaLISA Alzheimer's disease amyloid beta basal forebrain |
| title | A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential |
| title_full | A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential |
| title_fullStr | A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential |
| title_full_unstemmed | A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential |
| title_short | A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential |
| title_sort | novel process driving alzheimer s disease validated in a mouse model therapeutic potential |
| topic | 5XFAD acetylcholinesterase alphaLISA Alzheimer's disease amyloid beta basal forebrain |
| url | https://doi.org/10.1002/trc2.12274 |
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