A Preliminary Study on the Effects of LPS Stimulation on ERK Phosphorylation and DUSP4 Expression in BV2 Cells

Abstract

Alzheimer’s Disease (AD), a terminal neurodegenerative condition which causes progressive memory loss and cognitive impairment, affects tens of millions of patients worldwide and their families. There is currently no cure, and treatments are largely palliative. The condition may be inherited in an autosomal-dominant manner, but the vast majority of cases result from a complex mix of genetic and environmental factors. AD is characterized by amyloid beta plaques and tau neurofibrillary tangles in affected areas of the brain. These lesions interact with the signaling networks in the neural environment to drive pathogenesis. A new drug, aducanumab, was granted accelerated approval last year by the FDA, largely on the basis of its ability to reduce amyloid plaque burden. However, amyloidosis is only part of AD pathogenesis. New directions, including the identification of VGF and its genetic network as a key driver of AD, allow for a more integrated approach to AD. Of note is the presence of DUSP4, a regulator of the MAP kinase group of major signaling pathways in the VGF network. The current study investigates the effect of LPS stimulation on BV2, a murine microglial line, on MAP kinase ERK signaling and DUSP4 expression. LPS was found to induce ERK phosphorylation in under 1 hour. The data on DUSP4 protein expression are inconclusive. However, further investigation of the ERK/DUSP4 relationship in microglia may lead to elucidation of the complex mechanisms underlying AD.