Activation of hippo pathway enhances Tau mediated neurodegeneration in Alzheimer’s Disease
Prajakta D. Deshpande, Caitlin R. Masters
Alzheimer’s Disease (AD), the most common progressive neurodegenerative disorder, marked by memory loss and cognition issues, has no cure till date. AD is caused by extracellular accumulation of amyloid-beta 42 (Aβ42) plaques and intracellular accumulation of neurofibrillary tangles (NFTs). NFTs are formed from the hyperphosphorylated forms of Tau, a microtubule-associated protein (MAP). The biological function of this MAP is determined by its degree of phosphorylation. The dephosphorylated version of Tau is responsible for promoting the assembly of microtubules and maintaining their structure, while hyperphosphorylated Tau becomes toxic and loses its ability to assemble microtubules. Intracellular accumulation of NFTs trigger aberrant signaling resulting in neuronal cell death by unknown mechanism(s). We employed the Gal4/UAS system in Drosophila melanogaster to misexpress human Tau mutant (TauR406W) within the developing fly retina, exhibiting AD-like neuropathology. Using candidate based forward genetic screening, we identified hippo (hpo) as one of the genetic modifiers of GMR>TauR406W reduced eye phenotype. Gain-of-function of hpo in GMR>TauR406W background worsens the neurodegenerative phenotype, whereas the loss-of-function of hpo in the GMR>TauR406W background rescues it. Here, we propose that modulating hippo pathway members will affect Tau mediated neurodegeneration in AD.
Madhuri Kango-Singh, Amit Singh
Primary Advisor's Department
Stander Symposium project, College of Arts and Sciences
United Nations Sustainable Development Goals
Good Health and Well-Being
"Activation of hippo pathway enhances Tau mediated neurodegeneration in Alzheimer’s Disease" (2022). Stander Symposium Projects. 2427.