کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8328191 1540205 2018 43 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Can any “non-specific charge modification within microtubule binding domains of Tau” be a prerequisite of the protein amyloid aggregation? An in vitro study on the 1N4R isoform
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Can any “non-specific charge modification within microtubule binding domains of Tau” be a prerequisite of the protein amyloid aggregation? An in vitro study on the 1N4R isoform
چکیده انگلیسی
The aggregation of Tau into amyloid fibrils is a hallmark of neurodegenerative diseases such as Alzheimer's disease (AD). Compared to the Aβ peptide, tau pathology more closely tracks changes in brain function that are responsible for the onset of early symptoms in AD. Tau belongs to the class of intrinsically disordered protein and folds into an ordered β-structure during aggregation, a process that appears in many cases to be preceded by hyperphosphorylation of Tau monomers. Although Tau fibrils can be formed by heparin-induced aggregation of un-phosphorylated recombinant Tau, it is important to understanding the paradox of Tau's random-like conformations and aggregation propensity. In this study, to look into the effect of charge neutralization on Tau aggregation propensity, solvent accessible lysine residues were chemically acetylated/pseudo-phosphorylated. All Tau variants did not aggregate in the absence of the polyanionic factor; however, in contrast to the wild-type protein, acetylated and pseudo-phosphorylated variants were not able to aggregate even in the presence of the polyanionic cofactor. These aggregation incompetent Tau variants may be good analogs for the phosphorylated Tau, to explore more about the exact role of the phosphorylated Tau monomers in AD progress.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Biological Macromolecules - Volume 109, 1 April 2018, Pages 188-204
نویسندگان
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