Dataset Information

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 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.

SUBMITTER: Greenfield SA

PROVIDER: S-EPMC8983808 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential.

Greenfield Susan A SA Cole Gregory M GM Coen Clive W CW Frautschy Sally S Singh Ram P RP Mekkittikul Marisa M Garcia-Ratés Sara S Morrill Paul P Hollings Owen O Passmore Matt M Hasan Sibah S Carty Nikisha N Bison Silvia S Piccoli Laura L Carletti Renzo R Tacconi Stephano S Chalidou Anna A Pedercini Matthew M Kroecher Tim T Astner Hubert H Gerrard Philip A PA

Alzheimer's & dementia (New York, N. Y.) 20220405 1

<h4>Introduction</h4>The neuronal mechanism driving Alzheimer's disease (AD) is incompletely understood.<h4>Methods</h4>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.<h4>Results</h4>T14 increases in AD brains as the disease progresses and is conspicuous in 5XFAD mice, where its immunoreactivity corresponds to t ...[more]

PMID: 35415206

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Dataset Information

A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential.

Introduction

Methods

Results

Discussion

Publications

A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential.

Similar Datasets

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