测量小分子 Hsp70 激动剂体外和体内活性的试验。

IF 2.6 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS Analytical biochemistry Pub Date : 2024-11-09 DOI:10.1016/j.ab.2024.115712

Olivia Shapiro , Clara Woods , Amanda M. Gleixner , Sara Sannino , Marilyn Ngo , Michael D. McDaniels , Peter Wipf , Neil A. Hukriede , Christopher J. Donnelly , Jeffrey L. Brodsky

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引用次数: 0

摘要

Hsp70 可防止蛋白质聚集并具有细胞保护作用，但持续过量表达 Hsp70 会带来问题。因此，我们开发了能增强 Hsp70 活性的小分子激动剂。由于检测激动剂需要进行繁琐的试验，我们开发了基于细胞的试验和体内试验，通过这些试验可以量化 Hsp70 激活对疾病造成的影响。其中一种试验使用光遗传系统，该系统可控制 TDP-43 包涵体的形成；第二种试验使用斑马鱼急性肾损伤（AKI）模型。这些互补性试验将有助于未来鉴定新的 Hsp70 激动剂以及其他优化的 MAL1-271 衍生物的工作。

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Assays to measure small molecule Hsp70 agonist activity in vitro and in vivo

Hsp70 prevents protein aggregation and is cytoprotective, but sustained Hsp70 overexpression is problematic. Therefore, we characterized small molecule agonists that augment Hsp70 activity. Because cumbersome assays were required to assay agonists, we developed cell-based and in vivo assays in which disease-associated consequences of Hsp70 activation can be quantified. One assay uses an optogenetic system in which the formation of TDP-43 inclusions can be controlled, and the second assay employs a zebrafish model for acute kidney injury (AKI). These complementary assays will facilitate future work to identify new Hsp70 agonists as well as optimized agonist derivatives.

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来源期刊

Analytical biochemistry 生物-分析化学

CiteScore

5.70

自引率

0.00%

发文量

283

审稿时长

44 days

期刊介绍： The journal''s title Analytical Biochemistry: Methods in the Biological Sciences declares its broad scope: methods for the basic biological sciences that include biochemistry, molecular genetics, cell biology, proteomics, immunology, bioinformatics and wherever the frontiers of research take the field. The emphasis is on methods from the strictly analytical to the more preparative that would include novel approaches to protein purification as well as improvements in cell and organ culture. The actual techniques are equally inclusive ranging from aptamers to zymology. The journal has been particularly active in: -Analytical techniques for biological molecules- Aptamer selection and utilization- Biosensors- Chromatography- Cloning, sequencing and mutagenesis- Electrochemical methods- Electrophoresis- Enzyme characterization methods- Immunological approaches- Mass spectrometry of proteins and nucleic acids- Metabolomics- Nano level techniques- Optical spectroscopy in all its forms. The journal is reluctant to include most drug and strictly clinical studies as there are more suitable publication platforms for these types of papers.