Cryptic exon inclusion in TDP-43 proteinopathies:opportunities and challenges  

作　　者：Lorena Decker Sonja Menge Axel Freischmidt 

机构地区：[1]Department of Neurology,Ulm University,Ulm,Germany

出　　处：《Neural Regeneration Research》2025年第7期2003-2004,共2页中国神经再生研究（英文版）

基　　金：supported by the Deutsche Forschungsgemeinschaft(DFG;grant#521487152)(to AF)。

摘　　要：TDP-43 proteinopathies and cryptic exons:Transactive response DNA binding protein of 43 kDa(TDP-43)is a ubiquitously expressed RNA/DNA binding protein crucial for coding and non-coding RNA metabolism including transcription,splicing,transport,translation,and turnover.TDP-43 shuttles between the nucleus and cytoplasm,but is predominantly localized in the nucleus.Neurodegenerative diseases(NDs)may be accompanied by nuclear loss and possible cytoplasmic accumulation and aggregation of TDP-43 in vulnerable neurons and beyond.This neuropathology is the hallmark of most individuals suffering from amyotrophic lateral sclerosis(ALS),frontotemporal dementia(FTD)with TDP-43-immunoreactive pathology(FTD-TDP),limbic-predominant age-related TDP-43 encephalopathy(LATE)and Perry syndrome,but also coexists with the primary pathology in subsets of patients suffering from other NDs,such as Alzheimer’s disease,Lewy body dementias,or Huntington’s disease.Variants in the gene encoding TDP-43(TARDBP)are the cause of ALS and/or FTD in some rare cases substantiating the importance of this protein in aging neurons.It is still controversial if loss of nuclear,or increased cytoplasmic and/or aggregating TDP-43 is more harmful to neurons(Nag and Schneider,2023).Recently,the role of nuclear TDP-43 in repressing the inclusion of intronic sequences,named cryptic exons(CEs),into mature mRNAs gained much attention.

关 键 词：HUNTINGTON METABOLISM TDP 

分 类 号：R741[医药卫生—神经病学与精神病学]