SCF ‐Slimb is critical for Glycogen synthase kinase‐3β‐mediated suppression of TAF15‐induced neurotoxicity in Drosophila

In this study, we show in TAF15‐expressingDrosophila models that Shaggy/GSK3 β inhibition in neuronal cells leads to a reduction in TAF15 levels, and SCFslimb is a critical regulator for Shaggy/GSK3 β‐mediated suppression of TAF15‐induced toxicity inDrosophila. This presents in vivo evidence supporting GSK3 β inhibition as an agent in neuroprotection against TAF15‐linked proteinopathies. AbstractAmyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder characterized pathologically by motor neuron degeneration and associated with aggregation of RNA ‐binding proteins. TATA‐binding protein‐associated factor 15 (TAF15) accumulates as cytoplasmic aggregates in neuronal cells, and clearance of these aggregates is considered a potential therapeutic strategy for ALS. However, the exact pathogenic mechanism of TAF15‐induced neurotoxicity remai ns to be elucidated. Glycogen synthase kinase‐3 (GSK‐3) plays a critical role in the protection of ALS pathology. In the present study, we use a transgenic fly model over‐expressing human TAF15 to study the protective effects of Shaggy/GSK3β on TAF15‐induced neuronal toxicity inDrosophila brain. Transgenic flies were examined for locomotor activity and lithium treatment. The expression level and solubility of TAF15 were assessed with western blotting, whereas immunohistochemistry was used to assess TAF15 aggregation inDrosophila brain. We have revealed that Shaggy/GSK3 β was abnormally activated in n...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research