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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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