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A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential.
Greenfield, Susan A; Cole, Gregory M; Coen, Clive W; Frautschy, Sally; Singh, Ram P; Mekkittikul, Marisa; Garcia-Ratés, Sara; Morrill, Paul; Hollings, Owen; Passmore, Matt; Hasan, Sibah; Carty, Nikisha; Bison, Silvia; Piccoli, Laura; Carletti, Renzo; Tacconi, Stephano; Chalidou, Anna; Pedercini, Matthew; Kroecher, Tim; Astner, Hubert; Gerrard, Philip A.
Afiliación
  • Greenfield SA; Culham Science Centre Neuro-Bio Ltd Abingdon UK.
  • Cole GM; Department of Neurology & Medicine USA and Veterans Affairs Healthcare System David Geffen School of Medicine at UCLA Los Angeles USA.
  • Coen CW; Faculty of Life Sciences & Medicine King's College London London UK.
  • Frautschy S; Department of Neurology & Medicine USA and Veterans Affairs Healthcare System David Geffen School of Medicine at UCLA Los Angeles USA.
  • Singh RP; Department of Neurology & Medicine USA and Veterans Affairs Healthcare System David Geffen School of Medicine at UCLA Los Angeles USA.
  • Mekkittikul M; Department of Neurology & Medicine USA and Veterans Affairs Healthcare System David Geffen School of Medicine at UCLA Los Angeles USA.
  • Garcia-Ratés S; Culham Science Centre Neuro-Bio Ltd Abingdon UK.
  • Morrill P; Culham Science Centre Neuro-Bio Ltd Abingdon UK.
  • Hollings O; Culham Science Centre Neuro-Bio Ltd Abingdon UK.
  • Passmore M; Culham Science Centre Neuro-Bio Ltd Abingdon UK.
  • Hasan S; Culham Science Centre Neuro-Bio Ltd Abingdon UK.
  • Carty N; Manfred Eigen Campus Evotec SE Hamburg Germany.
  • Bison S; Aptuit Evotec (Verona) Srl Verona Italy.
  • Piccoli L; Aptuit Evotec (Verona) Srl Verona Italy.
  • Carletti R; Aptuit Evotec (Verona) Srl Verona Italy.
  • Tacconi S; Aptuit Evotec (Verona) Srl Verona Italy.
  • Chalidou A; Aptuit Evotec (Verona) Srl Verona Italy.
  • Pedercini M; Aptuit Evotec (Verona) Srl Verona Italy.
  • Kroecher T; Manfred Eigen Campus Evotec SE Hamburg Germany.
  • Astner H; Aptuit Evotec (Verona) Srl Verona Italy.
  • Gerrard PA; Aptuit Evotec (Verona) Srl Verona Italy.
Alzheimers Dement (N Y) ; 8(1): e12274, 2022.
Article en En | MEDLINE | ID: mdl-35415206
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Alzheimers Dement (N Y) Año: 2022 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Alzheimers Dement (N Y) Año: 2022 Tipo del documento: Article