title: Discovery of compounds that will prevent tau pathology.
abstract: Tau is certainly a reasonable target for the development of compounds to prevent neurofibrillary pathology, particularly in the fronto-temporal dementias. Although the mechanism of the filamentous accumulations remains unclear, sufficient knowledge is in place to move forward with high throughput screens. In fact, the development of compounds from such screens will ultimately be the only way to validate the target. The dichotomy for such screens is that in vitro screens are easier to design, but require more assumptions as to the mechanism, in contrast to cell-based screens that are more difficult to design, but make fewer assumptions about mechanism. We have designed a moderate throughput for tau binding that relies on fluorescence detection in living cells and an in vitro cdk5/p25 tau phosphorylation high throughput screen.
authors.affiliation: Harvard Medical School, Brigham and Women's Hospital, 77 Ave. Louis Pasteur, Boston, MA 02115, USA. kosik@cnd.bwh.harvard.edu
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kosik
authors.forename: Jae
authors.initials: J
authors.lastname: Ahn
authors.forename: Ross
authors.initials: R
authors.lastname: Stein
authors.forename: Li-An
authors.initials: LA
authors.lastname: Yeh
mesh_terms: D000818:Animals; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D024801:Tauopathies / Q000517:prevention & control*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; C089495:neuronal Cdk5 activator (p25-p35); D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases