由此可见,目前研究热点依旧集中在TDP-43 GOF的角度(异常聚集的TDP-43是致病的“坏人”,所以要清除病变的TDP-43来治病);基于TDP-43 LOF角度(即TDP-43是“好人”,疾病是因为好人太少而导致,所以需要补充缺失的TDP-43)的药物研究则...
具有mRNA转录、翻译、剪接和稳定性等多种功能(20,21).肌萎缩侧索硬化症(ALS)危险因素的筛选表明,TDP-43的异位表达与人类胚胎肾(HEK)293T细胞报告系统L1逆转录酶活性降低有关(22).在果蝇TDP-43的过度表达或敲除(KO)可能损害Dicer-2/Ago2介导的小干扰RNA(siRNA)...
[9] ALS News Today. (n.d.). ALS Gene Therapy SOL-257 Targeting TDP-43 Shows Promise in Mouse Model. Retrieved fromhttps://alsnewstoday.com/news/als-gene-therapy-sol-257-targeting-tdp-43-shows-promise-mouse-model/ [10] ALS News Today. (n.d.). Vectory Raises Millions to Advance AL...
2022年2月23日，美国斯坦福大学Aaron D. Gitler研究组以及美国梅奥医学中心Leonard Petrucelli研究组合作在Nature上发表了文章TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A；同期，英国伦敦大学学院皇后广场神经研究所Pietro Fratta研究组以及美国国立卫生研究院神经疾病和中风研究所Michael E. Ward...
[8] Buratti E. Targeting TDP-43 proteinopathy with drugs and drug-like small molecules. Br J Pharmacol. 2021 Mar;178(6):1298-1315. [9] ALS News Today. (n.d.). ALS Gene Therapy SOL-257 Targeting TDP-43 Shows Promise in Mouse Model. Retrieved from https://alsnewstoday.com/news/als...
Protein TDP-43 keeps genetic zombies at bay Reference: Yingzi Hou et al, TDP-43 chronic deficiency leads to dysregulation of transposable elements and gene expression by affecting R-loop and 5hmC crosstalk, Cell Reports (2024). DOI: 10.1016/j.celrep.2023.113662...
TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations. J Neuropathol Exp Neurol 2007; 66: 152-7.Neumann M , Mackenzie IR , Cairns NJ , Boyer PJ , Markesbery WR , Smith CD , Taylor JP , Kretzschmar HA , Kimonis VE , Forman MS ( 2007 ) TDP-43 in ...
通过这种方法检测发现,m6A修饰的RNA位点大部分位于TDP43底物的编码区。GO(gene ontology)分析显示,甲基化的TDP43底物RNA中,很多与核孔复合体组分相关,这与ALS病理发生有密切联系。 进一步分析DART-seq数据,研究人员还发现了一个有趣的现象。编码...
基因别名:1190002A23Rik; ALS10; C85084; TARDBP; TDP-43; TDP43 UniProt ID:(Human) Q13148,(Mouse) Q921F2 Entrez Gene ID:(Human) 23435,(Mouse) 230908,(Rat) 298648 功能 nucleotide bindingtranscriptional activator activity, RNA polymerase II distal enhancer sequence-specific bindingdouble-stranded ...
TDP-43 has since been shown to bind RNA as well as DNA, and have multiple functions in transcriptional repression, translational regulation and pre-mRNA splicing. For instance, it is reported to regulate alternate splicing of the CTFR gene. In 2006 Neumann et al. found that hyperphosphorylated...