Autor: |
Oyarce-Pezoa, Sebastián, Rucatti, Guilherme Gischkow, Muñoz-Carvajal, Francisco, Sanhueza, Nicole, Gomez, Wileidy, Espinoza, Sandra, Leiva, Mario, García, Nicolás, Ponce, Daniela P., SanMartín, Carol D., Rojas-Rivera, Diego, Salvadores, Natalia, Behrens, Maria I., Woehlbier, Ute, Calegaro-Nassif, Melissa, Sanhueza, Mario |
Předmět: |
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Zdroj: |
Scientific Reports; 10/10/2023, Vol. 13 Issue 1, p1-12, 12p |
Abstrakt: |
Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by protein accumulation in the brain as a main neuropathological hallmark. Among them, Aβ42 peptides tend to aggregate and create oligomers and plaques. Macroautophagy, a form of autophagy characterized by a double-membrane vesicle, plays a crucial role in maintaining neuronal homeostasis by degrading protein aggregates and dysfunctional organelles as a quality control process. Recently, DEF8, a relatively uncharacterized protein, has been proposed as a participant in vesicular traffic and autophagy pathways. We have reported increased DEF8 levels in lymphocytes from mild cognitive impairment (MCI) and early-stage AD patients and a neuronal profile in a murine transgenic AD model. Here, we analyzed DEF8 localization and levels in the postmortem frontal cortex of AD patients, finding increased levels compared to healthy controls. To evaluate the potential function of DEF8 in the nervous system, we performed an in silico assessment of its expression and network profiles, followed by an in vivo evaluation of a neuronal Def8 deficient model using a Drosophila melanogaster model of AD based on Aβ42 expression. Our findings show that DEF8 is an essential protein for maintaining cellular homeostasis in the nervous system, and it is upregulated under stress conditions generated by Aβ42 aggregation. This study suggests DEF8 as a novel actor in the physiopathology of AD, and its exploration may lead to new treatment avenues. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
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