학술논문
A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential
Document Type
Report
Author
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.
Source
Alzheimer’s & Dementia: Translational Research & Clinical Interventions. April 2022, Vol. 8 Issue 1
Subject
Language
English
Abstract
BACKGROUND The basic mechanism driving Alzheimer's disease (AD), as well as Parkinson disease and motor neuron disease, may be the deleterious activation in the maturity of a signaling system that [...]
: 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.
: 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.