Abstract #4306
Pharmocological treatment with HDAC-6 Inhibitor (ACY-738) recovers Alzheimer's phenotype in APP/PS1 mice
Tabassum Majid 1,2 , Deric Griffin 1,2 , Zachary Criss II 1 , Asante Hatcher 3 , Matthew Jarpe 4 , and Robia Pautler 2,5
1
Translational Biology and Molecular
Medicine, Baylor College of Medicine, Houston, Texas,
United States,
2
Molecular
Physiology & Biophysics, Baylor College of Medicine,
Houston, TX, United States,
3
Department
of Neuroscience, Baylor College of Medicine, Houston,
TX, United States,
4
Acetylon
Pharmaceuticals, Boston, MA, United States,
5
Translational
Biology and Molecular Medicine, Baylor College of
Medicine, Houston, TX, United States
The development of HDAC-6 inhibitors for Alzheimer's
disease (AD) therapy has been met with limited success
due to lack of selectivity and brain bioavailibility. In
this study, we demonstrate the effectiveness of a novel,
selective HDAC-6 inhibitor (ACY-738) treatment in the
APP/PS1 mouse model of AD. We demonstrate improvements
in axonal transport (MEMRI), learning and memory assays,
post-translational protein modifications of the
microtubule, and amyloid pathology. We believe this
pre-clinical proof of concept study contributes to
recent evidence of specific, selective HDAC-6 inhibitor
therapies in neurodegenerative diseases.
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