Insulin degrading enzyme as a downstream target of stress and growth factors signaling cascades: implications for Alzheimer`s disease interventions

LEAL, MC; GHIGULLY, M; CASTAÑO, EM; MORELLI, L

Pinamar, Argentina

Congreso; PABMB 10th Congress, SAIB 41th Annual Meetin and SAN 20th Annual Meeting.; 2005

Insulin-Degrading Enzyme (IDE) is one of the proteins that has been demonstrated to play a key role in degrading amyloid b (Ab) in vitro and in vivo, raising the possibility of upregulating IDE as an approach to reduce Ab. Little is known, however, about the cellular and molecular regulation of IDE protein. The aim of this work was to evaluate the role of stress and growth factors (GF) cell signaling pathways on IDE protein and mRNA expression levels. In this study, primary astrocytes from new-born rats, human THP-1 monocytic cells and N2a mouse neuroblastoma cells (wild type and over-expressing Ab) were used as cellular models in providing mechanisms by which IDE may be regulated in the brain. Cell-cultures were subjected to stressor agents such as Ab exposure at 1 mM concentration (sub-optimal for neurotoxicity), 1 mM H2O2 treatment, serum deprivation and in vitro replicative aging according to standard protocols. Immunofluorescence confocal microscopy was used to investigate sub-cellular IDE expression. IDE transcripts levels were monitored by RT-PCR. The findings in this study tentatively suggest that GF and stress signaling may strongly induce IDE expression in the brain. We propose that IDE may be modulated as a novel therapeutic intervention in Alzheimer`s disease. (PICT2002 10599, IIRG 03-5312)