The ER-unfolded protein response modulates neurotoxicity induced by dementia-associated amyloid peptides

CASTAÑO EM; BELFIORI CARRASCO LF; GARCIA CI; MARCORA MS; MORELLI L; BOCAI NI

BUENOS AIRES

Congreso; Reunión Conjunta de Sociedades de Biociencias, LXII Reunión Cientifíca Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2017

Alzheimer?s disease (AD), the most common neurodegenerativedisorder and Familiar Danish Dementia (FDD), a rare autosomaldominant disease, shares some features, including amyloid accumulation,ADan and Aβ respectively, progressive dementia andpresence of neurofibrillary tangles.Growing evidences suggest that amyloid accumulation inducesER stress in early stages of neurodegeneration. Disturbed ERhomeostasis engages an adaptive reaction known as the unfoldedprotein response (UPR) that protects the cell against toxic misfoldedproteins.IRE1 activation, the most conserved UPR branch, includes theunconventional splicing of XBP1, a transcription factor that up-regulatesgenes related to protein folding (including BIP) and ER-mediateddegradation.In order to study the relation between UPR and amyloid peptidesneurotoxicity we used transgenic Drosophila melanogaster lines.The neuronal expression of ADan caused impairment in climbingability in 3-day old flies, while in Ab42 flies the impairment beganat 21 days as compared to BRI2-23, a non-amyloidogenic control(ANOVA RM, p