INVESTIGATING THE ROLE OF SIGNALING KINASES IN DEMENTIA

Abstract

Chronic neuroinflammation and widespread cellular death are key characteristic hallmarks of dementia. An isoform-specific involvement of JNK3 and FynT kinases in neuroinflammation and cellular death have been demonstrated. Characterization of JNK3 levels was conducted in a neuropathologically characterized cohort of Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB), the two main subtypes of LBD. We observed a significant decrease in JNK3 in LBD and this decrease may have resulted from a compensatory effect in response to higher neuropathological burden as well as synaptic loss in the diseased brain. Pyroptosis is a pro-inflammatory cellular death pathway that may contribute to overall inflammatory responses in the brain. To date, the signaling mediators regulating pyroptosis have not been well-elucidated. Using immortalized normal human astrocytes (iNHA) stably transfected FynT wild type (FynT-WT) or kinase dead construct (FynT-KD) clones, our study findings revealed an inhibitory role of FynT on DHA-induced pyroptosis.