| Full text | |
| Author(s): |
Lima, Raquel S.
;
Carrettiero, Daniel C.
;
Ferrari, Merari F. R.
Total Authors: 3
|
| Document type: | Journal article |
| Source: | MOLECULAR BIOLOGY REPORTS; v. N/A, p. 13-pg., 2022-05-25. |
| Abstract | |
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) | |
| FAPESP's process: | 11/06434-7 - Degradation of hyperphosphorylated tau and organelles trafficking during neurodegenerative processes linked to protein aggregation in hypoccampal cell cultures |
| Grantee: | Merari de Fátima Ramires Ferrari |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center |
| Grantee: | Mayana Zatz |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 18/07592-4 - The role of quality control mechanisms in the loss of proteostasis in age-dependent neurodegenerative diseases |
| Grantee: | Merari de Fátima Ramires Ferrari |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 17/24722-6 - Chaperones machines to combat protein aggregation in Parkinson's Disease |
| Grantee: | Raquel de Souza Lima |
| Support Opportunities: | Scholarships abroad - Research Internship - Master's degree |
| FAPESP's process: | 16/04409-9 - Analysis of autophagy and the role of co-chaperone bag-2 upon protein aggregates in neurodegenerative diseases |
| Grantee: | Raquel de Souza Lima |
| Support Opportunities: | Scholarships in Brazil - Master |