期刊
CLINICAL AND TRANSLATIONAL MEDICINE
卷 12, 期 5, 页码 -出版社
JOHN WILEY & SONS LTD
DOI: 10.1002/ctm2.818
关键词
ALS; FTD; TDP-43; UNC13A
资金
- NIH
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases characterized by depletion of the RNA-binding protein TDP-43. TDP-43 plays a vital role in repressing the inclusion of cryptic exons during RNA splicing. Understanding and targeting these cryptic splicing events may have significant implications for the diagnosis and treatment of ALS and FTD.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two devastating human neurodegenerative diseases. A hallmark pathological feature of both diseases is the depletion of the RNA-binding protein TDP-43 from the nucleus in the brain and spinal cord of patients. A major function of TDP-43 is to repress the inclusion of cryptic exons during RNA splicing. When it becomes depleted from the nucleus in disease, this function is lost, and recently, several key cryptic splicing targets of TDP-43 have emerged, including STMN2, UNC13A, and others. UNC13A is a major ALS/FTD risk gene, and the genetic variations that increase the risk for disease seem to do so by making the gene more susceptible to cryptic exon inclusion when TDP-43 function is impaired. Here, we discuss the prospects and challenges of harnessing these cryptic splicing events as novel therapeutic targets and biomarkers. Deciphering this new cryptic code may be a touchstone for ALS and FTD diagnosis and treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据