D18 Small extracellular vesicles in response to mutant huntingtin. (12th September 2022)

• Record Type: Journal Article
• Authors: Tartaglia, Natayme Rocha; Farina, Francesca; Martin-Jaular, Lorena; Loew, Damarys; Dingli, Florent; Brouillet, Emmanuel; Théry, Clotilde; Neri, Christian
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 93(2022)Supplement 1
• Page Start: A26
• Page End: A26
• Publication Date: 2022-09-12
• Subjects: Extracellular vesicles -- Huntington's disease -- cellular models; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2022-ehdn.74
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background: Extracellular vesicles (EVs) are a variety of lipid bilayer nanoparticles released by cells that have important roles in intercellular communication by sharing bioactive molecules. EVs play an emerging role in the progression of neurodegenerative diseases (ND). However, EVs are highly heterogeneous and the effects of ND insults on specific EV sub-types remain to be understood. Here, we investigated key features of small EVs (SEVs) in mouse and human cell models of HD pathogenesis, with a focus on SEVs of endosomal origin. Methods: We purified SEVs from conditioned medium of striatal cells derived from HD knock-in mice and neural cells derived from human HD induced pluripotent stem cells. SEVs were purified using size exclusion chromatography (SEC), followed by nanoparticle tracking analysis (NTA), total protein dosage, western blot analysis using a panel of EV markers that includes tetraspanins, and quantitative mass spectrometry analysis. Results: We found that SEVs undergo profound modifications in response to mutant huntingtin, including impaired secretion, reduced tetraspanin levels, protein-content remodeling, suggesting that HD neural cells may reprogram the biogenesis and secretion of SEVs of endosomal origin, during neuronal differentiation. Conclusion: Our data uncover SEV-remodeling as an early-stage response to ND insults such as mutant huntingtin, providing a rationale for investigating the value of SEVs as a source of HD biomarkers.