{"title":"Isoform-paralog specificity and tissue-dependent vulnerabilities in neurological disorders.","authors":"Karina Hernandez-Quijada, Kenneth Y Kwan","doi":"10.1101/gad.353864.126","DOIUrl":null,"url":null,"abstract":"<p><p>A long-standing observation in studies of neurological disorders is that broadly expressed disease genes can cause dysfunctions that are limited to certain brain regions or cell types. In this issue of <i>Genes & Development,</i> Lee et al. (doi:10.1101/gad.353596.125) address the mystery of this selective vulnerability by studying ATXN1-CIC interactions implicated in spinocerebellar ataxia type 1. They provide compelling evidence that specific ATXN1 paralogs preferentially interact with specific CIC isoforms tissue-dependently. Whereas ATXN1-CIC-L complexes regulate hippocampal gene expression and learning, ATXN1L-CIC-S complexes regulate lung alveolarization, postnatal survival, and hydrocephalus risk. This work thus demonstrates the potential contribution of isoform-paralog specificity to tissue-specific vulnerabilities in neurological disorders.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"1175-1177"},"PeriodicalIF":7.4000,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13431150/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes & development","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1101/gad.353864.126","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
A long-standing observation in studies of neurological disorders is that broadly expressed disease genes can cause dysfunctions that are limited to certain brain regions or cell types. In this issue of Genes & Development, Lee et al. (doi:10.1101/gad.353596.125) address the mystery of this selective vulnerability by studying ATXN1-CIC interactions implicated in spinocerebellar ataxia type 1. They provide compelling evidence that specific ATXN1 paralogs preferentially interact with specific CIC isoforms tissue-dependently. Whereas ATXN1-CIC-L complexes regulate hippocampal gene expression and learning, ATXN1L-CIC-S complexes regulate lung alveolarization, postnatal survival, and hydrocephalus risk. This work thus demonstrates the potential contribution of isoform-paralog specificity to tissue-specific vulnerabilities in neurological disorders.
期刊介绍：
Genes & Development is a research journal published in association with The Genetics Society. It publishes high-quality research papers in the areas of molecular biology, molecular genetics, and related fields. The journal features various research formats including Research papers, short Research Communications, and Resource/Methodology papers.
Genes & Development has gained recognition and is considered as one of the Top Five Research Journals in the field of Molecular Biology and Genetics. It has an impressive Impact Factor of 12.89. The journal is ranked #2 among Developmental Biology research journals, #5 in Genetics and Heredity, and is among the Top 20 in Cell Biology (according to ISI Journal Citation Reports®, 2021).
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
