P1‐180: ABNORMAL DJ‐1 EXPRESSION IN ALZHEIMER'S DISEASE AND ITS IMPACT ON SYNAPTIC MRNA TRANSLATION AND FUNCTION

• DOI: 10.1016/j.jalz.2019.06.735
• Publication Date: 2019-10-18T10:45:36Z
• Authors: Ayse Uneri; Farr Niere; Suzanne Craft; Dirk C. Keene; Tao Ma; Kimberly F. Raab-...
• Keywords: Postsynaptic density; Immunoprecipitation

Alzheimer's Disease (AD) is a progressive synaptic disorder and the 6th leading cause of death in United States. To date, there still no effective long term therapy or cure. Parkinson Protein 7 (DJ-1) protein that was recently identified as potential biomarker for AD. Our recent work has predicted DJ-1 translational hub, an RNA binding can potentially determine expression other proteins important learning memory. Of note, DJ-1's RNA-binding properties, mRNA-targets, physiological functions at synapse have remained largely unexplored. if aberrantly expressed AD, western blot analysis synaptoneurosomes from AD rodent models (APP/PS1deltaE9) postmortem human patients, well appropriate controls, were performed. Further, postsynaptic densities prepared 3xTG mouse model putative target-mRNAs are also disrupted we first mRNAs contain DJ-1-binding sites. Putative mRNA-targets analyzed using consensus sequence DJ-1. Candidate verified by RNA-immunoprecipitation specific antibody against (Santa Cruz) hippocampal lysates. increased synapses prefrontal cortices post-synaptic mice, compared to controls. Notably, voltage-gated calcium channel (VGCC) subunit alpha-2 delta-2 (α2δ2), coded gene CACNA2D2, 14–26 sites distributed throughout its mRNA. RNA-IP followed semi-quantitative PCR CACNA2D2 mRNA-target Furthermore, α2δ2 remarkably reduced patients models. The increase corresponding reduction levels suggest repressor may be pathogenesis progression. Further underway identify DJ-1-target characterize their function