| Literature DB >> 34917762 |
Taylor D Pobran1, Lauren M Forgrave1, Yu Zi Zheng1, John G K Lim1, Ian R A Mackenzie1,2, Mari L DeMarco1,3.
Abstract
Transactive response DNA-binding protein 43 kDa (TDP-43) is a highly conserved and widely expressed protein in human tissues that regulates nucleic acid processing. In frontotemporal dementia and amyotrophic lateral sclerosis, however, TDP-43 forms insoluble aggregates in central nervous tissues. These pathological deposits of TDP-43 have been primarily studied by ligand binding, namely western blot analysis, and, thus, methods with greater structural resolution are needed to aid in our understanding of the pathological processes associated with TDP-43 misfolding and aggregation. Toward this goal, we have developed a selective and multiplex method for the detection and characterization of TDP-43 using liquid chromatography tandem mass spectrometry. As proof-of-concept, the method was applied to the detection and characterization of TDP-43 in human cell lines and human brain tissue.Entities:
Keywords: ALS, amyotrophic lateral sclerosis; Amyotrophic lateral sclerosis; Biomarkers; FTD, frontotemporal dementia; FTLD, frontotemporal lobar degeneration; Frontotemporal dementia; LC, liquid chromatography; MRM, multiple reaction monitoring; MS/MS, triple quadrupole mass spectrometer; Mass spectrometry; Multiple reaction monitoring; PTM, post-translational modification; S/N, signal to noise ration; TDP-43, transactive response DNA-binding protein 43 kDa; Transactive response DNA-binding protein 43 kDa; ePAR, expected peak area ratio; p, detergent-insoluble fraction; rec, recombinant; s, detergent-soluble fraction
Year: 2019 PMID： 34917762 PMCID： PMC8669462 DOI： 10.1016/j.clinms.2019.07.003
Source DB: PubMed Journal: Clin Mass Spectrom ISSN： 2213-8005