Recently, researchers from the Institute of Biophysics, Chinese Academy of Sciences, Northwestern University Feinberg School of Medicine, Tsinghua University, Yale University, National Nanoscience Center of the Chinese Academy of Sciences and others "Nature Structural & Molecular Biology" published a research paper on the TDP-43 gene mutation caused its protein aggregation and neurotoxicity.
Professor Wu Ying from the National "Thousand Talents Program" of the Institute of Biophysics of the Chinese Academy of Sciences and young teacher Xu Qi from the School of Basic Medical Sciences of Tsinghua University are co-corresponding authors of this article. This work was supported by the Ministry of Science and Technology 973 Program and the Chinese Academy of Sciences.
TDP-43 is a versatile DNA and RNA binding protein that functions in the process of RNA transcription, alternative splicing, and mRNA stability regulation in cells. Ubiquitinated protein inclusion bodies can be detected in neurons and glial cells in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTLD) in the spinal cord or brain damage area, characterized by TDP-43 Sexual composition. In familial or sporadic ALS cases, more than 30 TDP-43 mutations have been identified, and they are mostly concentrated in the glycine-rich region at the C-terminus of the protein. So far, the mechanism by which TDP-43 forms protein aggregates and its relationship with neurodegenerative diseases are unclear.
Prior to this, Wu Ying's group had published a research paper in the Proceedings of the National Academy of Sciences (PNAS) in the United States, reporting on the research work of the TDP-43 protein disease fruit fly model, which proved to be overexpressed in different types of neurons in fruit flies Human-derived TDP-43 protein can cause characteristics similar to neurodegenerative diseases. Based on this Drosophila model, Guo Weirui et al. Found that overexpression of wild-type and A315T mutant TDP-43 protein in Drosophila motor neurons can cause neuronal axon and cell swelling, and lead to Drosophila larval motor ability and Reduced viability. The C-terminal fragment of TDP-43 containing the A315T mutation site has sequence similarity with prion protein. Structural prediction of this fragment revealed that it has a tendency to form β-sheet. Synthetic wild-type and A315T mutant peptides can form fiber-like precipitates visible in electron microscope in vitro. Both are toxic to neurons cultured in vitro and cause cell death, and the toxicity of A315T mutant peptides is more than that of wild-type Strong.
These results prove that the wild type and A315T mutant of TDP-43 have differences in biochemical properties and structure, showing the similarity of the biochemical and structural properties of the C-terminal fragment of TDP-43 and prion protein, and suggesting that the pathology The lateral propagation of TDP-43 toxic peptides produced under conditions between nerve cells may be one of the molecular mechanisms that cause ALS and FTLD diseases.
6Ft Folding Table,Folding Dining Table,Foldable Rectangular Table,Rectangular Banquet Table
Zhejiang Lifan Furniture.Co.,Ltd , https://www.lffoldingtable.com