TDP-43 is a widely expressed nuclear protein that binds both DNA and RNA. While shuttling between nucleus and cytoplasm, it helps regulate many aspects of RNA processing, such as splicing, trafficking, stabilization, and miRNA production.

2018年3月6日 · Consistent with TDP-43 autoregulation, a decrease in endogenous murine levels was observed in transgenic mice. Transgene expression was highest in the brain and spinal cord with very low levels observed in other tissues. At birth, the TDP-43 Q331K mice were indistinguishable from non-Tg littermates.

2019年5月1日 · Instead, TDP-43 inclusions crowd her limbic regions. This would be a typical case of limbic-predominant age-related TDP-43 encephalopathy (LATE), a common neurodegenerative disease christened by an international cadre of pathologists, clinicians, and epidemiologists in a consensus report published April 30 in Brain.

2018年3月6日 · Protein levels of human TDP-43 were highest in the brain, spinal cord, and muscle, with lower levels in the liver and kidney, mimicking endogenous expression patterns. Despite modest overexpression, these mice develop quite robust TDP-43 pathology, including an accumulation of cytoplasmic TDP-43 in motor neurons in the spinal cord by 10 months ...

2020年9月9日 · The TDP-43 construct lacked a nuclear localization signal, keeping it cytoplasmic. Again, poly(GR) aggregated with TDP-43, but poly(GA) did not (see image above). By mutating various regions of TDP-43, the authors determined that its ability to bind poly(GR) did not depend on its RNA-binding motifs, nor on its sticky C-terminal tail.

2024年10月31日 · To investigate TDP-43 proteinopathy, joint first authors Muzi Du and Suleyman Akerman turned to a mouse model first developed by Leonard Petrucelli at the Mayo Clinic in Jacksonville, Florida (Chew et al., 2019). Du and Akerman injected an adenoviral vector carrying the C9ORF72 gene into the ventricles of newborn wild-type mice.

2018年1月9日 · Phosphorylated and cleaved TDP-43 in ALS, FTLD and other neurodegenerative disorders and in cellular models of TDP-43 proteinopathy. Neuropathology. 2010 Apr;30(2):170-81. PubMed. Nonaka T, Kametani F, Arai T, Akiyama H, Hasegawa M. Truncation and pathogenic mutations facilitate the formation of intracellular aggregates of TDP-43.

2016年2月4日 · TDP-43 (Wt-TAR6/6) Paper Citations. Wils H, Kleinberger G, Janssens J, Pereson S, Joris G, Cuijt I, Smits V, Ceuterick-de Groote C, Van Broeckhoven C, Kumar-Singh S. TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci U S A. 2010 Feb 23;107(8 ...

2018年3月6日 · The cytotoxic 25 kDA C-terminal fragment of TDP-43 also increased in an age-dependent manner in both the brain and spinal cord. Evidence of cytoskeletal abnormalities was observed in the brain and spinal cord, including aggregates of the intermediate filament peripherin, a hallmark of degenerating motor neurons in ALS.

2019年6月5日 · TDP-43 protein was primarily nuclear, however, some cytoplasmic TDP-43 was observed in neurons of the spinal cord, brainstem, and cortex. Phosphorylated TDP-43 (at serine 403 and 404) was frequently seen in motor neurons …