Jose F Abisambra
University of Kentucky, USA
Scientific Tracks Abstracts: Neurochem Neuropharm
Tauopathies are a group of more than twenty known debilitating neurodegenerative disorders that affect nearly eight million people in the United States. Currently, there is no cure for tauopathies, and there are temporary and limited benefits to current therapeutic strategies. The endoplasmic reticulum (ER) stress sensor PERK (protein kinase R-like ER kinase) has been identified as a participant in the pathogenesis and progression of tauopathies. However, the mechanism by which the PERK pathway causes neuronal dysfunction is still unknown. In this study, we treated rTg4510 tau transgenic mice at a stage when tau pathology is rampant and cognitive function is impaired with a novel and potent PERK inhibitor. The treatment significantly reduced hyper phosphorylated tau species and led to improvement of neuronal function, as determined with a sensitive and innovative imaging technique called manganese-enhanced magnetic resonance imaging (MEMRI) with quantitative R1 mapping. We also found that PERK inhibition mediated these improvements via a pathway that is independent of eIF2�±. Our results show a novel mechanism of PERK-mediated tau phosphorylation that potentiates pathogenesis and progression of tau pathology. Future efforts aim to delineate the mechanism ruling the tau-PERK relationship. Finally, this study suggests that PERK is a viable therapeutic target to ameliorate neuronal function in tauopathies.
Jose F Abisambra completed his PhD and Post-doctoral studies in 2010 and 2013, respectively, at the University of South Florida. He is Principal Investigator in the Tau Research Lab at the University of Kentucky. He published more than 23 papers in reputed journals and serves as Editorial Board Member of the Journal of Alzheimer’s Disease. His work is supported by the National Institutes of Health (NINDS, NIA, NIGMS, NCATS, and NIMHD), the US Department of Defense, and the Alzheimer’s Association.
Email: joe.abisambra@uky.edu
