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O5‐04‐05: A NEW THERAPEUTIC STRATEGY FOR TAUOPATHIES: DISCOVERY OF HIGHLY POTENT BRAIN PENETRANT PROTAC TM DEGRADER MOLECULES THAT TARGET PATHOLOGIC TAU PROTEIN SPECIES
Author(s) -
Cacace Angela M.,
Chandler J.,
Flanagan J.J.,
Berlin M.,
Cadelina G.,
Pizzano J.,
Bookbinder M.,
Crews C.M.,
Crew A.P.,
Taylor I.,
Houston J.
Publication year - 2019
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.2019.06.4856
Subject(s) - tauopathy , neurodegeneration , ubiquitin ligase , tau protein , proteolysis , ubiquitin , protein degradation , chemistry , biochemistry , microbiology and biotechnology , biology , neuroscience , alzheimer's disease , medicine , pathology , disease , enzyme , gene
tissue, but not in seeding incompetent tau from control or AD brain tissue. Immunoprecipitation of ubiquitinated proteins resulted in a seeding competent preparation that was highly abundant in tau. Conclusions: Our data show that charge neutralizing modifications are present in the core region of AD tau. Based on these results and the known cryo electron-microscopy structure of tau filaments, we propose a model where accumulation of charge neutralizing PTMs promotes the formation of tau aggregates.