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针对慢性炎症作为预防阿尔茨海默病策略的临床前狨猴模型

Preclinical Marmoset Model for Targeting Chronic Inflammation as a Strategy to Prevent Alzheimer's Disease.

作者信息

Philippens Ingrid H C H M, Langermans Jan A M

机构信息

Animal Science Department, Biomedical Primate Research Centre (BPRC), Lange Kleiweg 161, 2288 GJ Rijswijk, The Netherlands.

Department Population Health Sciences, Unit Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.

出版信息

Vaccines (Basel). 2021 Apr 15;9(4):388. doi: 10.3390/vaccines9040388.

Abstract

Due to the aging population, modern society is facing an increasing prevalence of neurological diseases such as Alzheimer's disease (AD). AD is an age-related chronic neurodegenerative disorder for which no satisfying therapy exists. Understanding the mechanisms underlying the onset of AD is necessary to find targets for protective treatment. There is growing awareness of the essential role of the immune system in the early AD pathology. Amyloidopathy, the main feature of early-stage AD, has a deregulating effect on the immune function. This is reciprocal as the immune system also affects amyloidopathy. It seems that the inflammatory reaction shows a heterogeneous pattern depending on the stage of the disease and the variation between individuals, making not only the target but also the timing of treatment important. The lack of relevant translational animal models that faithfully reproduce clinical and pathogenic features of AD is a major cause of the delay in developing new disease-modifying therapies and their optimal timing of administration. This review describes the communication between amyloidopathy and inflammation and the possibility of using nonhuman primates as a relevant animal model for preclinical AD research.

摘要

由于人口老龄化,现代社会正面临着诸如阿尔茨海默病(AD)等神经疾病患病率不断上升的问题。AD是一种与年龄相关的慢性神经退行性疾病,目前尚无令人满意的治疗方法。了解AD发病的潜在机制对于寻找保护性治疗靶点至关重要。人们越来越意识到免疫系统在早期AD病理过程中的重要作用。淀粉样病变是早期AD的主要特征,对免疫功能具有失调作用。这是相互的,因为免疫系统也会影响淀粉样病变。炎症反应似乎根据疾病阶段和个体差异呈现出异质性模式,这使得治疗靶点和治疗时机都很重要。缺乏能够忠实地再现AD临床和致病特征的相关转化动物模型是开发新的疾病修饰疗法及其最佳给药时机延迟的主要原因。这篇综述描述了淀粉样病变与炎症之间的相互作用,以及使用非人类灵长类动物作为AD临床前研究相关动物模型的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d17d/8071309/279a65237195/vaccines-09-00388-g001.jpg

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