Abstract Details Title The Relationship Between GSK3?eta Activity and TDP-43 Mediated Neuritis in Neurodegenerative Diseases Topic Aging, Dementia, and Behavioral Neurology Presentation(s) P6 - Poster Session 6 (8:00 AM-9:00 AM) Poster/Presentation Number 9-005 Objective We want to see if regulating GSK3β activity could weaken cystic TDP-43 intermediate neuroinflammatory in degenerative diseases. Background TDP-43-positive inclusions have also been reported to be associated with the hippocampal CA1 Lewy-body pathology of familial PD patients bearing a Parkin mutant suggesting that there is likely a link between Parkin and TDP-43. Also, It is known that loss of the nuclear RNA binding protein TAR DNA binding protein-43 (TDP-43) into cytoplasmic inclusions is the strongest correlate to neurodegeneration in frontotemporal degeneration (FTD) and amyotrophic lateral sclerosis (ALS). TDP-43, TAF15, and FUS are DNA/RNA binding proteins, and these lead to neurodegenerative disease when inducing cytoplasmic aggregates. Selective expression of TDP-43 in rat astrocytes also leads to non-cell autonomous neuronal toxicity. TDP-43 is ubiquitously expressed in many tissues and cell types, including glial cells of the central nervous system. Glycogen Synthase Kinase 3β (GSK3β) is a Serine/Threonine protein kinase that phosphorylate either threonine or serine and participates in a variety of cellular processes such glycogen metabolism, gene transcription, apoptosis and microtubule stability. Design/Methods To identify the mechanism of neuroinflammatory induction through over-expression of GSK3β in astrocytes using Shaggy which is the homolog of GSK3β in drosophila model. Results 1. GSK3β / Shaggy enzyme activity was increased in TDP-43-induced drosophila degenerative model.2. Inhibition of Shaggy restored the abnormal wing posture in TDP-43-induced drosophila degenerative model.3. Inhibition of Shaggy restored the locomotor activity of adult flies in TDP-43-induced drosophila degenerative model.4. Inhibition of GSK3β restored the neuromuscular junction defects in TDP-43-induced drosophila degenerative model.5. Cytoplasmic TDP-43 was decreased by the knockdown of GSK3β6. Astrocyte-derived TDP43 aggregates are spread and propagation to neurons. Conclusions We could see that to regulate GSK3β activity might be weaken cystic TDP-43 intermediate neuroinflammatory in degenerative diseases. Authors/Disclosures Eu Jene Choi, MD, PhD(c) PRESENTER Dr. Choi has nothing to disclose.