两种新型 DnaJ 伴侣蛋白 CG5001 和 P58IPK 调节亨廷顿病相关聚集物的致病性。

Two novel DnaJ chaperone proteins CG5001 and P58IPK regulate the pathogenicity of Huntington's disease related aggregates.

机构信息

Department of Biotechnology, Savitribai Phule Pune University, Ganeshkhind, Pune, 411007, India.

Indian Institute of Science and Educational Research (IISER), Dr. Homi Bhabha Road, Pashan, Pune, 411008, India.

出版信息

Sci Rep. 2024 Sep 6;14(1):20867. doi: 10.1038/s41598-024-71065-3.

DOI:10.1038/s41598-024-71065-3

PMID:39242711

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11379882/

Abstract

Huntington's disease (HD) is a rare neurodegenerative disease caused due to aggregation of Huntingtin (HTT) protein. This study involves the cloning of 40 DnaJ chaperones from Drosophila, and overexpressing them in yeasts and fly models of HD. Accordingly, DnaJ chaperones were catalogued as enhancers or suppressors based on their growth phenotypes and aggregation properties. 2 of the chaperones that came up as targets were CG5001 and P58IPK. Protein aggregation and slow growth phenotype was rescued in yeasts, S2 cells, and Drosophila transgenic lines of HTT103Q with these overexpressed chaperones. Since DnaJ chaperones have protein sequence similarity across species, they can be used as possible tools to combat the effects of neurodegenerative diseases.

摘要

亨廷顿病（HD）是一种罕见的神经退行性疾病，由亨廷顿蛋白（HTT）的聚集引起。本研究涉及从果蝇中克隆 40 种 DnaJ 伴侣蛋白，并在酵母和 HD 果蝇模型中过表达它们。因此，根据它们的生长表型和聚集特性，将 DnaJ 伴侣蛋白分类为增强子或抑制剂。作为靶点的 2 种伴侣蛋白是 CG5001 和 P58IPK。过表达这些伴侣蛋白后，酵母、S2 细胞和携带 HTT103Q 的果蝇转基因系中的蛋白聚集和生长缓慢表型得到了挽救。由于 DnaJ 伴侣蛋白在物种间具有蛋白质序列相似性，因此它们可以作为对抗神经退行性疾病影响的可能工具。