A role of PTPN21 in neuron survival and degeneration

Abstract

BACKGROUND: Alzheimer’s disease (AD) chronically leads to dramatic neuronal loss, as they undergo apoptotic cell death, a direct consequence of the b-amyloid deposition or due to damage to their axon. The nervous system has an extremely poor regenerative capabilities and the adult brain’s potential at replacing neurons and regrowing axons is very limited. Therefore, recovering from AD faces many challenges. Moreover, the secondary response at the site establishes a toxic environment, quashing any tentative repair. Previously, our published results revealed that PTPN21 promotes neuron migration and survival via Elk-1 transcription factor, one of the transcription factors of Presenilin 1 (PS1). Henceforth, in this study we explore the potential role of PTPN21 in pathological changes in AD. METHODS: We used our established model of overexpressing PTPN21 or functional lost mutant for PTPN21 and expose the cells to high levels of amyloid precursor protein (APP), and quantify the levels of b-amyloid (1-42 & 1-40), PS1 and other AD’s markers using immunoblotting and ELISA assays. RESULTS: PTPN21 reduces the secretion of b-amyloid and importantly, our preliminary data showing significant PTPN21-dependent reduction of both PS1 levels and human b-Amyloid (1-42). Furthermore, PTPN21 promotes neuron survival through NRG3 pathway. CONCLUSIONS: To this end, our current study uncovered a link between PTPN21 and a specific mechanism of via PS1 to reduce b-amplyoid production, of which, might help to slow the progression of AD.