BAG2 prevents Tau hyperphosphorylation and increases p62/SQSTM1 in cell models of neurodegeneration

Autor(es)

Lima, Raquel S. ; Carrettiero, Daniel C. ; Ferrari, Merari F. R.

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR BIOLOGY REPORTS; v. N/A, p. 13-pg., 2022-05-25.

Resumo

Background Protein aggregates are pathological hallmarks of many neurodegenerative diseases, however the physiopathological role of these aggregates is not fully understood. Protein quality control has a pivotal role for protein homeostasis and depends on specific chaperones. The co-chaperone BAG2 can target phosphorylated Tau for degradation by an ubiquitin-independent pathway, although its possible role in autophagy was not yet elucidated. In view of this, the aim of the present study was to investigate the association among protein aggregation, autophagy and BAG2 levels in cultured cells from hippocampus and locus coeruleus as well as in SH-SY5Y cell line upon different protein aggregation scenarios induced by rotenone, which is a flavonoid used as pesticide and triggers neurodegeneration. Methods and results The present study showed that rotenone exposure at 0.3 nM for 48 h impaired autophagy prior to Tau phosphorylation at Ser199/202 in hippocampus but not in locus coeruleus cells, suggesting that distinct neuron cells respond differently to rotenone toxicity. Rotenone induced Tau phosphorylation at Ser199/202, together with a decrease in the endogenous BAG2 protein levels in SH-SY5Y and hippocampus cell culture, which indicates that rotenone and Tau hyperphosphorylation can affect this co-chaperone. Finally, it has been shown that BAG2 overexpression, increased p62/SQSTM1 levels in cells from hippocampus and locus coeruleus, stimulated LC3II recycling as well as prevented the raise of phosphorylated Tau at Ser199/202 in hippocampus. Conclusions Results demonstrate a possible role for BAG2 in degradation pathways of specific substrates and its importance for the study of cellular aspects of neurodegenerative diseases. (AU)

• Processo FAPESP: 11/06434-7 - Degradação da proteína tau hiperfosforilada e tráfego de organelas durante processos neurodegenerativos associados à agregação protéica em cultura de células do hipocampo
• Beneficiário: Merari de Fátima Ramires Ferrari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 18/07592-4 - Papel dos mecanismos de controle de qualidade na perda da proteostase em doenças neurodegenerativas dependentes da idade
• Beneficiário: Merari de Fátima Ramires Ferrari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/24722-6 - Maquinaria de chaperonas para combater a agregação protéica na Doença de Parkinson
• Beneficiário: Raquel de Souza Lima
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Mestrado
• Processo FAPESP: 16/04409-9 - Análise do processo autofágico e ação da co-chaperona bag-2 sobre agregados proteicos típicos de doenças neurodegenerativas
• Beneficiário: Raquel de Souza Lima
• Modalidade de apoio: Bolsas no Brasil - Mestrado