MITOCHONDRIAL-ASSOCIATED ENDOPLASMIC RETICULUM MEMBRANES IN AMYLOID-β INDUCED NEURON DAMAGE

SAUD, V; KOTLER, ML; SARAVIA, FE; GOROJOD, RM; PORTE ALCON, S

Mar del Plata

Congreso; Reunión de Sociedades de Biociencias 2022; 2022

Alzheimer´s disease (AD) is the most common type of dementia. The progressive neuronal degeneration?beginning in the hippocampus?is accompanied by Amyloid-ss peptides (Ass) aggregation in amyloid plaques. The accumulation of insoluble protein aggregates has been associated with autophagy impairment and neuronal cell death. The association between the membranes of endoplasmic reticulum (ER) and mitochondria (M) (MAMs) are crucial for calcium homeostasis, lipid synthesis and autophagy, among other biological functions. MAMs alterations are associated with different pathologies, including neurodegenerative disease. Moreover, it has been proposed that the metabolic disturbances seen in AD are consequence of an altered ER-M communication. Our goal is to study the link between MAMs alterations and autophagy dysregulation as the leading causes of hippocampal neuronal loss induced by β-amyloid. HT22 hippocampal cells were exposed for 24 h to a sub-toxic concentration (Crystal Violet assay) of fibrillar Ass peptides (2 µM Assf). Confocal microscopy analysis of GFP-Sec61β (ER marker) and DsRed2Mito (M marker) revealed that exposure to Assf reduces ER-M contacts (M1, p