In summary, our data suggest that TDP43 exacerbates inflammatory activation of astrocytes in NMOSD through upregulating the mtDNA/cGAS/STING signaling pathway. Therefore, targeting TDP43 represents a compelling therapeutic strategy for NMOSD.Zhuhe Liu...
5月17日,PLOS Genetics 期刊在线发表了中国科学院生物物理研究所吴瑛研究组题目为TDP-43 induces m...阅读全文 日本熊本大学魏范研准教授、东京大学铃木勉教授的研究小组最新研究发现,一种被称作牛磺酸的功能性氨基酸在线粒体内外蛋白质的生产和保质中具有重要作用,实验表明,通过特定的化学物质维持蛋白质质量,可以改善...
TDP-43 is also known to associate with the Optic atrophy-1 protein (OPA1)-mitofilin complex10, which is critical for mitochondria fusion, cristae integrity, and mtDNA maintenance6,7,8. These data suggest additional platelet-related mechanisms by which TDP-43 neurotoxicity may be conveyed through...
Finally, we document elevated levels of the specific cGAS signaling metabolite cGAMP in spinal cord samples from patients, which may be a biomarker of mtDNA release and cGAS/STING activation in ALS. Our results identify mtDNA release and cGAS/STING activation as critical determinants of TDP-43-...
TDP-43 overexpression increases polycistronic transcripts of L- and H-strand mtDNA. (a) Relative band intensities of mt-tRNAs in total RNA extracted from DAP-TDP-43–expressing T-REx 293 cells (harvested at 0, 24, and 48 h after induction with doxycycline, Dox) were quantified by norther...
lonp1也是一个dna结合蛋白,参与线粒体dna(mtdna)完整性的维持及基因表达调控。因此,lonp1在线粒体蛋白质量控制(qualitycontrol,qc)中起至关重要的重要。lon蛋白酶的单个亚基由3个结构域组成,n端是蛋白底物识别区,中间是aaa+元件负责atp结合和水解,c端的p-结构域负责蛋白底物降解。大脑眼牙耳骨骼综合症(cerebral,...
Oxidative stress triggers neuronal injury and mouse pain sensitization by up-regulating TDP-43 to activate mtDNA-cGAS/STING pathway To investigate the role and possible mechanisms of transactive response DNA binding protein 43 (TDP-43) in mediating neuronal ... LI Li,P Huang,J Cui - 《Journal...
qPCR was utilized to measure the release of mtDNA. Immunostaining was conducted to observe intracellular expression of TDP-43, and Calcein AM staining was employed to evaluate mPTP opening status. ⑥To elucidate the role of TDP-43 in neuropathic pain (NP), 24 healthy SPF male C57BL/6J mice ...
are not fully understood.A recent study by Yu et al.is proposing that noxious neuroinflammatory stimulation associated with TDP-43 pathology is caused by excess TDP-43 penetration into mitochondria followed by cytosolic release of mitochondrial DNA(mtDNA)and activation of the cGAS/STING immune sensor...
FTD/ALS-linked CHCHD10 mutations and TDP-43 inclusions similarly induce mitochondrial defects in respiration, fusion/fission, mtDNA stability, and cristae structure, while sizeable amounts of cytoplasmic TDP-43 aggregates are found in mitochondria. However, the mechanistic link between CHCHD10 and ...