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P2‐131: p53 family members induce the phosphorylation of human tau in cultured mammalian cells
Author(s) -
Hooper Claudie,
Killick Richard,
Lovestone Simon
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1204
Subject(s) - phosphorylation , tauopathy , epitope , tau protein , gene isoform , microbiology and biotechnology , biology , microtubule , chemistry , neurodegeneration , alzheimer's disease , biochemistry , medicine , immunology , gene , antibody , disease
to selected curcumin derivatives and approved tetracyclines for their tau antiaggregatory properties and their affinity to fibrillar beta-amyloid in several assays and cellular models. The most potent fluorescent compounds were evaluated for beta-amyloid/tau PHF selectivity by fluorescence microscopy of human AD probes. Methods: Lead Optimization of PTHs. Several diverse PTH analogues were obtained by variation of the substituents R1-R4 to explore a preliminary SAR. Fluorescent substituents were incorporated without significantly compromising in vitro activity. Results: Tau-biased ligands with enhanced affinity to tau paired helical filaments over beta-amyloid were identified by a panel of protein aggregation assays and fluorescence microscopy of human AD preparations. Conclusions: Phenylthiazolylhydrazides are potent inhibitors of tau-aggregation. The fluorescence microscopy of human AD preparation suggests a binding to growth-relevant sites of tau aggregates.