Talk abstracts
Talk on Tuesday 04:30-04:45pm submitted by Sarah Kaye
The E3 Ubiquitin Ligase IDOL Regulates Microglial Phagocytosis in Alzheimer’s Disease
Sarah Kaye (Neuroscience Graduate Program)
Abstract:
Alzheimer’s Disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of disease associated microglia (DAM) surrounding amyloid beta (Aβ) plaques. Previously, we discovered a novel E3 ubiquitin ligase IDOL that serves as a major post-transcriptional regulator of three brain ApoE receptors. We showed that both genetic deletion and pharmacological inhibition of IDOL led to a reduction in the number and size of Aβ plaques and increased expression of genes associated with DAM phenotype. Here we show acute knockdown of IDOL increases microglial phagocytosis of Aβ plaques and the expression of DAM markers, including ApoE and TREM2. Additionally, long-term inhibition of IDOL reduced the number and size of Aβ plaques, decreased plaque-associated neuritic dystrophy, and improved cognitive function in human APP knock-in mice. These findings suggest that inhibition of IDOL may serve as a potential therapeutic strategy to delay of the progression of Alzheimer’s disease.
Keywords: Alzheimers, Microglia