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用于临床前测试应用的5XFAD小鼠模型的综合评估:一项MODEL-AD研究。

Comprehensive Evaluation of the 5XFAD Mouse Model for Preclinical Testing Applications: A MODEL-AD Study.

作者信息

Oblak Adrian L, Lin Peter B, Kotredes Kevin P, Pandey Ravi S, Garceau Dylan, Williams Harriet M, Uyar Asli, O'Rourke Rita, O'Rourke Sarah, Ingraham Cynthia, Bednarczyk Daria, Belanger Melisa, Cope Zackary A, Little Gabriela J, Williams Sean-Paul G, Ash Carl, Bleckert Adam, Ragan Tim, Logsdon Benjamin A, Mangravite Lara M, Sukoff Rizzo Stacey J, Territo Paul R, Carter Gregory W, Howell Gareth R, Sasner Michael, Lamb Bruce T

机构信息

Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States.

Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States.

出版信息

Front Aging Neurosci. 2021 Jul 23;13:713726. doi: 10.3389/fnagi.2021.713726. eCollection 2021.

Abstract

The ability to investigate therapeutic interventions in animal models of neurodegenerative diseases depends on extensive characterization of the model(s) being used. There are numerous models that have been generated to study Alzheimer's disease (AD) and the underlying pathogenesis of the disease. While transgenic models have been instrumental in understanding AD mechanisms and risk factors, they are limited in the degree of characteristics displayed in comparison with AD in humans, and the full spectrum of AD effects has yet to be recapitulated in a single mouse model. The Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease (MODEL-AD) consortium was assembled by the National Institute on Aging (NIA) to develop more robust animal models of AD with increased relevance to human disease, standardize the characterization of AD mouse models, improve preclinical testing in animals, and establish clinically relevant AD biomarkers, among other aims toward enhancing the translational value of AD models in clinical drug design and treatment development. Here we have conducted a detailed characterization of the 5XFAD mouse, including transcriptomics, electroencephalogram, imaging, biochemical characterization, and behavioral assessments. The data from this study is publicly available through the AD Knowledge Portal.

摘要

在神经退行性疾病动物模型中研究治疗干预措施的能力取决于对所使用模型的全面表征。已经产生了许多用于研究阿尔茨海默病(AD)及其潜在发病机制的模型。虽然转基因模型有助于理解AD机制和风险因素,但与人类AD相比,它们所表现出的特征程度有限,并且AD的全部效应尚未在单一小鼠模型中得到重现。美国国立衰老研究所(NIA)组建了晚发性阿尔茨海默病模式生物开发与评估(MODEL-AD)联盟,以开发与人类疾病相关性更高的更强大的AD动物模型,规范AD小鼠模型的表征,改善动物的临床前测试,并建立临床相关的AD生物标志物,以及实现其他旨在提高AD模型在临床药物设计和治疗开发中的转化价值的目标。在此,我们对5XFAD小鼠进行了详细表征,包括转录组学、脑电图、成像、生化表征和行为评估。本研究的数据可通过AD知识门户公开获取。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f73b/8346252/7344e332c89f/fnagi-13-713726-g001.jpg

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