值得注意的是,没有检测到TDP-43果蝇的运动变化,提示TDP-43表达相关的睡眠紊乱与TDP-43的运动神经元毒性无关,是独立的睡眠调节机制。进一步分析显示,TDP-43和对照果蝇在夜间对机械睡眠剥夺的反应相似,并且在睡眠剥夺后表现出正常的补偿性睡眠增加(图2A和2B)...
这项研究中使用的小鼠模型包括TDP-43M337VBAC转基因小鼠和ATXN2 BAC转基因小鼠,并将常规C57BL/6J小鼠作为对照,从小鼠胚胎中提取脊髓,并分离脊髓运动神经元进行培养。将健康对照和携带ATXN2中等长度扩增的ALS患者来源的iPSCs诱导分化为人类脊髓运动神...
Expression of TDP-43 severely disrupts sleep, and the sleep deficit is rescued by Atx2 knockdown. Brain RNA sequencing revealed that Atx2 RNA interference regulates transcripts enriched for small-molecule metabolic signaling in TDP-43 brains. Focusing on these Atx2-regulated genes, we identified ...
Small-Molecule Modulation of TDP-43 Recruitment to Stress Granules Prevents Persistent TDP-43 Accumulation in ALS/FTD. Authors - Mark Y Fang View Article human IF Nat Commun NUP62 localizes to ALS/FTLD pathological assemblies and contributes to TDP-43 insolubility. Authors - Amanda M Gleixner Vi...
Interestingly, the RNA-binding protein (RBP), TAF15 which has been implicated in ALS was identified as a strong binder of Ataxin-2 in the condition of TDP-43 overexpression. Together, this study provides a comprehensive annotation of the Ataxin-2 and TDP-43 intera...
A study in yeast, flies and ALS patients suggests that antagonizing ATXN2's interaction with TDP-43 could be useful for treating the disease. Further details on the research, next steps and licensing status are discussed in the article.SciBX: Science-Business eXchange...
Intermediate-length repeat expansions in ATAXIN-2 (ATXN2) are the strongest genetic risk factor for amyotrophic lateral sclerosis (ALS). At the molecular level, ATXN2 intermediate expansions enhance TDP-43 toxicity and pathology. However, whether this triggers ALS pathogenesis at the cellular and ...
In spinal cord neurons of ALS patients, ATXN2 is abnormally localized; likewise, TDP-43 shows mislocalization in spinocerebellar ataxia type 2. To assess the involvement of ATXN2 in ALS, we analysed the length of the polyQ repeat in the ATXN2 gene in 915 ALS patients. We found that ...
Intermediate-length repeat expansions in ATAXIN-2 (ATXN2) are the strongest genetic risk factor for amyotrophic lateral sclerosis (ALS). At the molecular level, ATXN2 intermediate expansions enhance TDP-43 toxicity and pathology. However, whether this tr
Intriguingly, the deficiency of ATXN2 protein orthologs in yeastand flies rescues the neurodegeneration process triggered by TDP-43 and Ataxin-1 toxicity. To understand the molecular effectsof ATXN2 deficiency by unbiased approaches, we quantified the global proteome and metabolome of Atxn2-knock-out...