Neurodegenerative Disease-Associated TDP-43 Fragments Are Extracellularly Secreted with CASA Complex Proteins
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Cell Cultures
2.3. Subjects
2.4. EVs Isolation from NSC-34 Culture Medium
2.5. EVs Isolation from Plasma
2.6. Nanoparticle-Tracking Analysis
2.7. Transmission Electron Microscopy Analysis
2.8. Western Blot
2.9. Statistical Analysis
3. Results and Discussions
3.1. NSC-34 Cells-Secreted LVs and SVs Were Enriched in Insoluble TDP-43 Species That Were Almost Absent in Cells
3.2. EVs Contained PQC System Components Involved in the Intracellular Clearance of Insoluble TDP-43 Species
3.3. UPS Inhibition Increased The LVs Secretion of TDP-43 Species
3.4. Autophagy Blockage Did Not Affect Extracellular TDP-43 Species Release
3.5. The Simultaneous Blockage of UPS and Autophagy Increased the Extracellular LV-Mediated Release of TDP-35, TDP-25 and PQC System Components
3.6. FTLD Patients-Derived EVs Were Enriched in TDP-35 Fragments and Contained CASA Complex Components
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Casarotto, E.; Sproviero, D.; Corridori, E.; Gagliani, M.C.; Cozzi, M.; Chierichetti, M.; Cristofani, R.; Ferrari, V.; Galbiati, M.; Mina, F.; et al. Neurodegenerative Disease-Associated TDP-43 Fragments Are Extracellularly Secreted with CASA Complex Proteins. Cells 2022, 11, 516. https://doi.org/10.3390/cells11030516
Casarotto E, Sproviero D, Corridori E, Gagliani MC, Cozzi M, Chierichetti M, Cristofani R, Ferrari V, Galbiati M, Mina F, et al. Neurodegenerative Disease-Associated TDP-43 Fragments Are Extracellularly Secreted with CASA Complex Proteins. Cells. 2022; 11(3):516. https://doi.org/10.3390/cells11030516
Chicago/Turabian StyleCasarotto, Elena, Daisy Sproviero, Eleonora Corridori, Maria Cristina Gagliani, Marta Cozzi, Marta Chierichetti, Riccardo Cristofani, Veronica Ferrari, Mariarita Galbiati, Francesco Mina, and et al. 2022. "Neurodegenerative Disease-Associated TDP-43 Fragments Are Extracellularly Secreted with CASA Complex Proteins" Cells 11, no. 3: 516. https://doi.org/10.3390/cells11030516