Crosstalk between IMD and JNK pathways in Amyloid-beta 42 mediated neurodegeneration in Alzheimer’s Disease
Prajakta D. Deshpande, Samuel J. Shroder
Alzheimer's Disease (AD), affects 5.8 million people, is an incurable neurodegenerative disorder that leads to memory loss and reduced cognitive abilities. In AD, the miscleavage of the amyloid precursor protein (APP) results in the accumulation of Amyloid-beta 42 plaques outside neurons that triggers neuronal cell death. The mechanism for cell death is widely unknown and is currently being explored. In this study, Drosophila was used as a model system to mimic AD neuropathology by misexpressing human Aβ42 plaques in the developing eye of the Drosophila using the Gal4/UAS system. Misexpressing Aβ42 plaques triggers neuronal cell death and results in a glazed and reduced eye phenotype. It is known the immune deficiency (IMD) pathway plays a role in cell survival and the c-Jun N-terminal kinase (JNK) plays a role in cell death. Induction of the IMD pathway leads to the activation of NF-kB transcription factor Relish. Gain of function of Relish in the background of GMR> Aβ42, results in suppression of Aβ42 mediated neurodegeneration. Down regulation of Relish results in the smaller eye phenotype with necrotic spots. Activation of Relish is linked to proteasomal degradation of TGF-beta activated kinase 1 (TAK1), upstream component for JNK activation. So, it would be interesting to understand the crosstalk between Immune deficiency (IMD) pathway, and the c-Jun N-terminal kinase (JNK) pathway in Aβ42 mediated neurodegeneration.
Primary Advisor's Department
Stander Symposium project, College of Arts and Sciences
United Nations Sustainable Development Goals
Good Health and Well-Being
"Crosstalk between IMD and JNK pathways in Amyloid-beta 42 mediated neurodegeneration in Alzheimer’s Disease" (2020). Stander Symposium Projects. 1977.