Suppr超能文献

利用老年原代成年神经元、小胶质细胞和星形胶质细胞培养物进行形态学筛选以寻找新型神经治疗药物。

Morphological screens using aged primary adult neuronal, microglial, and astrocytic cultures to find novel neurotherapeutics.

作者信息

Sefiani Arthur

机构信息

Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, Bryan, TX, United States.

NeuroCreis, Inc., College Station, TX, United States.

出版信息

Front Cell Neurosci. 2023 Aug 23;17:1253192. doi: 10.3389/fncel.2023.1253192. eCollection 2023.

Abstract

The average age of a patient with neurotraumatic injuries or neurodegenerative diseases has been increasing worldwide. The preclinical live animal models used for neurotrauma and neurodegenerative diseases are typically young adults, failing to represent the age of humans in the clinic. This dichotomy in age between human populations and animal models is likely to impede the understanding of the pathological mechanisms of most neurological disorders and the translation of their respective promising therapies. This lack of cohesion between animal models and patients in the clinic begins prior to testing, it starts during the drug screening phase. Conventional screening methods typically involve the use of stem cell derived neural cells, with some researchers using embryonic derived neural cells instead. These cells lack the fundamental characteristics present in aged neural cells, such as age-induced changes in process length and branching in microglia and how astrocytes respond to various insults. Various technologies and techniques have been developed recently that can help researchers use age-appropriate neural cells for their drug discovery endeavors. The use of age-appropriate neural cells during screening phases is hypothesized to significantly increase the translation rate of the hits to the geriatric patients suffering from neurotraumatic and neurodegenerative diseases.

摘要

在全球范围内,患有神经创伤性损伤或神经退行性疾病的患者平均年龄一直在上升。用于神经创伤和神经退行性疾病研究的临床前活体动物模型通常是年轻成年动物,无法代表临床中人类的年龄。人类群体与动物模型之间的这种年龄差异可能会阻碍对大多数神经系统疾病病理机制的理解以及各自有前景疗法的转化。动物模型与临床患者之间缺乏连贯性在测试之前就已存在,始于药物筛选阶段。传统的筛选方法通常涉及使用干细胞衍生的神经细胞,一些研究人员则使用胚胎衍生的神经细胞。这些细胞缺乏老年神经细胞所具有的基本特征,例如随着年龄增长而在小胶质细胞中出现的突起长度和分支变化,以及星形胶质细胞对各种损伤的反应方式。最近已经开发出各种技术,可帮助研究人员在药物发现工作中使用与年龄相匹配的神经细胞。据推测,在筛选阶段使用与年龄相匹配的神经细胞可显著提高将筛选结果转化应用于患有神经创伤和神经退行性疾病老年患者的成功率。

相似文献

1
Morphological screens using aged primary adult neuronal, microglial, and astrocytic cultures to find novel neurotherapeutics.
Front Cell Neurosci. 2023 Aug 23;17:1253192. doi: 10.3389/fncel.2023.1253192. eCollection 2023.
3
Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models.
Stem Cell Reports. 2018 Mar 13;10(3):1030-1045. doi: 10.1016/j.stemcr.2018.01.021. Epub 2018 Feb 15.
4
Emerging three-dimensional neuronal culture assays for neurotherapeutics drug discovery.
Expert Opin Drug Discov. 2022 Jun;17(6):619-628. doi: 10.1080/17460441.2022.2061458. Epub 2022 Apr 4.
6
A primary neural cell culture model to study neuron, astrocyte, and microglia interactions in neuroinflammation.
J Neuroinflammation. 2020 May 11;17(1):155. doi: 10.1186/s12974-020-01819-z.
7
Liposomal clodronate selectively eliminates microglia from primary astrocyte cultures.
J Neuroinflammation. 2012 May 31;9:116. doi: 10.1186/1742-2094-9-116.
8
High-Throughput Phenotypic Screening of Human Astrocytes to Identify Compounds That Protect Against Oxidative Stress.
Stem Cells Transl Med. 2016 May;5(5):613-27. doi: 10.5966/sctm.2015-0170. Epub 2016 Mar 31.
9
Functional screening assays with neurons generated from pluripotent stem cell-derived neural stem cells.
J Biomol Screen. 2014 Jan;19(1):32-43. doi: 10.1177/1087057113501869. Epub 2013 Sep 9.
10
Chronic microglial inflammation promotes neuronal lactate supply but impairs its utilization in primary rat astrocyte-neuron co-cultures.
Biochem Biophys Res Commun. 2022 Jun 4;607:28-35. doi: 10.1016/j.bbrc.2022.03.122. Epub 2022 Mar 26.

引用本文的文献

1
Selective, Intrinsically Fluorescent Trk Modulating Probes.
ACS Chem Neurosci. 2024 Oct 2;15(20):3679-91. doi: 10.1021/acschemneuro.4c00290.

本文引用的文献

1
Age Stratification and Stroke Severity in the Telestroke Network.
J Clin Med. 2023 Feb 14;12(4):1519. doi: 10.3390/jcm12041519.
3
Microglia Phenotypes in Aging and Neurodegenerative Diseases.
Cells. 2022 Jun 30;11(13):2091. doi: 10.3390/cells11132091.
4
Mouse Models of Alzheimer's Disease.
Front Mol Neurosci. 2022 Jun 21;15:912995. doi: 10.3389/fnmol.2022.912995. eCollection 2022.
5
Comorbidity and age in the modelling of stroke: are we still failing to consider the characteristics of stroke patients?
BMJ Open Sci. 2020 Feb 24;4(1):e100013. doi: 10.1136/bmjos-2019-100013. eCollection 2020.
6
Biomaterial strategies for creating astrocyte cultures resembling astrocyte morphologies and phenotypes.
Curr Opin Biomed Eng. 2020 Jun;14:67-74. doi: 10.1016/j.cobme.2020.06.004. Epub 2020 Jul 4.
8
Comparing the Electrophysiology and Morphology of Human and Mouse Layer 2/3 Pyramidal Neurons With Bayesian Networks.
Front Neuroinform. 2021 Feb 18;15:580873. doi: 10.3389/fninf.2021.580873. eCollection 2021.
9
Models of Neurodegenerative Diseases.
Front Cell Dev Biol. 2020 May 13;8:328. doi: 10.3389/fcell.2020.00328. eCollection 2020.
10
A primary neural cell culture model to study neuron, astrocyte, and microglia interactions in neuroinflammation.
J Neuroinflammation. 2020 May 11;17(1):155. doi: 10.1186/s12974-020-01819-z.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验