The autophagy protein Def8 is altered in Alzheimer's disease and Aβ42-expressing Drosophila brains.

Autor: Oyarce-Pezoa S; Center for Resilience, Adaptation and Mitigation, Universidad Mayor, Temuco, Chile.; Laboratory of Autophagy and Neuroprotection, Vicerrectoría de Investigación, Universidad Mayor, Santiago, Chile.; PhD Program in Biomedicine, Universidad de los Andes, Santiago, Chile.; Center for Biomedical Research and Innovation (CiiB), Universidad de los Andes, Santiago, Chile., Rucatti GG; Center for Resilience, Adaptation and Mitigation, Universidad Mayor, Temuco, Chile.; Laboratory of Autophagy and Neuroprotection, Vicerrectoría de Investigación, Universidad Mayor, Santiago, Chile.; PhD Program in Neurobiology, Universidad Mayor, Santiago, Chile., Muñoz-Carvajal F; Center for Resilience, Adaptation and Mitigation, Universidad Mayor, Temuco, Chile.; PhD Program in Neurobiology, Universidad Mayor, Santiago, Chile., Sanhueza N; Center for Resilience, Adaptation and Mitigation, Universidad Mayor, Temuco, Chile., Gomez W; Laboratory of Autophagy and Neuroprotection, Vicerrectoría de Investigación, Universidad Mayor, Santiago, Chile.; PhD Program in Integrative Genomics, Universidad Mayor, Santiago, Chile., Espinoza S; Laboratory of Autophagy and Neuroprotection, Vicerrectoría de Investigación, Universidad Mayor, Santiago, Chile., Leiva M; Center for Resilience, Adaptation and Mitigation, Universidad Mayor, Temuco, Chile., García N; Center for Resilience, Adaptation and Mitigation, Universidad Mayor, Temuco, Chile., Ponce DP; Centro de Investigación Clínica Aplicada (CICA), Hospital Clínico Universidad de Chile, Santiago, Chile., SanMartín CD; Centro de Investigación Clínica Aplicada (CICA), Hospital Clínico Universidad de Chile, Santiago, Chile.; Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile., Rojas-Rivera D; Escuela de Biotecnología, Facultad de Ciencias, Universidad Mayor, Santiago, Chile.; Escuela de Tecnología Médica, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Santiago, Chile., Salvadores N; Center for Resilience, Adaptation and Mitigation, Universidad Mayor, Temuco, Chile.; Escuela de Medicina, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Temuco, Chile., Behrens MI; Centro de Investigación Clínica Aplicada (CICA), Hospital Clínico Universidad de Chile, Santiago, Chile.; Departamento de Neurociencia, Facultad de Medicina, Universidad de Chile, Santiago, Chile.; Departamento de Neurología y Psiquiatría, Clínica Alemana de Santiago, Santiago, Chile.; Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile., Woehlbier U; Center for Integrative Biology, Universidad Mayor, Santiago, Chile.; Escuela de Biotecnología, Facultad de Ciencias, Universidad Mayor, Santiago, Chile., Calegaro-Nassif M; Laboratory of Autophagy and Neuroprotection, Vicerrectoría de Investigación, Universidad Mayor, Santiago, Chile. melissa.calegaro@umayor.cl.; Escuela de Biotecnología, Facultad de Ciencias, Universidad Mayor, Santiago, Chile. melissa.calegaro@umayor.cl.; Escuela de Tecnología Médica, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Santiago, Chile. melissa.calegaro@umayor.cl., Sanhueza M; Center for Resilience, Adaptation and Mitigation, Universidad Mayor, Temuco, Chile. mario.sanhueza@umayor.cl.; Escuela de Medicina, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Temuco, Chile. mario.sanhueza@umayor.cl.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Oct 10; Vol. 13 (1), pp. 17137. Date of Electronic Publication: 2023 Oct 10.
DOI: 10.1038/s41598-023-44203-6
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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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