Publications by authors named "Csokova N"

Article Synopsis
  • The major component of Alzheimer's paired helical filaments (PHF) is the intrinsically disordered tau protein, which has made it difficult to determine the 3D structure of PHF using traditional methods like X-ray crystallography or NMR spectroscopy.
  • Researchers have successfully used a specific monoclonal antibody to imprint the in vivo structure of PHF into a recombinant tau protein, leading to the crystallization of a key fragment at high resolution.
  • This study suggests that the C-terminus of the tau protein plays a crucial role in the assembly of PHF and could pave the way for developing new drugs to inhibit Alzheimer's-related neurofibrillary changes.
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Tau protein, the major constituent of neurofibrillary tangles in Alzheimer's disease (AD) and related tauopathies, is classified as intrinsically disordered protein (IDP). IDPs in contrast to globular proteins contain high proportion of polar and charged amino acids in their sequence, which results in the absence of a well-defined three-dimensional structure of the free protein. Structural flexibility of IDPs is required to perform their important role in many cellular processes.

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Monoclonal antibody (mAb) MN423 recognizes Alzheimer's disease specific conformation of tau protein assembled into paired helical filaments (PHF). Since the three-dimensional structure of PHF is currently unavailable, the structure of MN423 binding site could provide important information about PHF conformation with the consequences for the Alzheimer's disease prevention and cure. Fab fragment of MN423 was prepared and purified.

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Truncated tau is of great interest because of its important role in neurofibrillary pathogenesis in Alzheimer's disease (AD). A major obstacle for characterization of detailed biochemical and biological properties of truncated tau species and their fragments has been the lack of reliable and quick purification methods. Uneven distribution of acidic and basic residues in tau determines that the N- and C-terminal tau fragments require entirely different purification conditions.

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The first confirmed evidence of scrapie in Slovakia was demonstrated in one sheep of the autochthonous Merino breed from the southeastern part of the country. The reported scrapie was diagnosed during compulsory transmissible spongiform encephalitis (TSE) screening of sheep over 9 months of age assigned for consumption. The positive ewe was 5-year-old, which did not show any clinical signs of scrapie.

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