Premium
P3‐182: SUBCELLULAR DISTRIBUTION OF PHOSPHODIESTERASE 4D (PDE4D) IN RHESUS MACAQUE DORSOLATERAL PREFRONTAL CORTEX: IMPLICATIONS FOR TAUOPATHY IN ALZHEIMER'S DISEASE
Author(s) -
Datta Dibyadeep,
Arnsten Amy F.T.
Publication year - 2018
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.2018.06.1540
Subject(s) - dorsolateral prefrontal cortex , neuroscience , tauopathy , phosphodiesterase , biology , prefrontal cortex , microbiology and biotechnology , psychology , neurodegeneration , medicine , disease , cognition , biochemistry , enzyme
used phosphatase activity assays to examine the effects of tau on PP1 enzymatic activity in vitro and from mammalian cell lysates. Results:We found that tau directly interacts with all isoforms of PP1. Interestingly, P301L displayed significantly enhanced interaction with PP1 compared to WT tau or the other two mutants. We also found that tau enhances PP1 phosphatase activity but with no significant differences in effect amongWTand FTDP-17 mutant versions of tau that were tested. Conclusions:The results presented here support a direct interaction between tau and PP1 that can enhance phosphatase activity. This supports our hypothesis that tau can activate PP1, which may have direct implications in taumediated axonal transport disruption and suggests some FTDP-17 mutations may confer toxicity through altering tau’s interaction with PP1, not through altering microtubule binding affinity and/ or aggregation propensity.