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Impact of α-Synuclein Fibrillar Strains and β-Amyloid Assemblies on Mouse Cortical Neurons Endo-Lysosomal Logistics

Endosomal transport and positioning cooperate in the establishment of neuronal compartment architecture, dynamics, and function, contributing to neuronal intracellular logistics. Furthermore, dysfunction of endo-lysosomal has been identified as a common mechanism in neurodegenerative diseases. Here,...

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Autores principales: Chou, Qiao-Ling, Alik, Ania, Marquier, François, Melki, Ronald, Treussart, François, Simonneau, Michel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118757/
https://www.ncbi.nlm.nih.gov/pubmed/35470226
http://dx.doi.org/10.1523/ENEURO.0227-21.2022
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author Chou, Qiao-Ling
Alik, Ania
Marquier, François
Melki, Ronald
Treussart, François
Simonneau, Michel
author_facet Chou, Qiao-Ling
Alik, Ania
Marquier, François
Melki, Ronald
Treussart, François
Simonneau, Michel
author_sort Chou, Qiao-Ling
collection PubMed
description Endosomal transport and positioning cooperate in the establishment of neuronal compartment architecture, dynamics, and function, contributing to neuronal intracellular logistics. Furthermore, dysfunction of endo-lysosomal has been identified as a common mechanism in neurodegenerative diseases. Here, we analyzed endo-lysosomal transport when α-synuclein (α-syn) fibrillar polymorphs, β-amyloid (Aβ) fibrils, and oligomers were externally applied on primary cultures of mouse cortical neurons. To measure this transport, we used a simple readout based on the spontaneous endocytosis in cultured neurons of fluorescent nanodiamonds (FNDs), a perfectly stable nano-emitter, and the subsequent automatic extraction and quantification of their directed motions at high-throughput. α-Syn fibrillar polymorphs, Aβ fibrils, and oligomers induce a 2-fold decrease of the fraction of nanodiamonds transported along microtubules, while only slightly reducing their interaction with cortical neurons. This important decrease in moving endosomes is expected to have a huge impact on neuronal homeostasis. We next assessed lysosomes dynamics, using LysoTracker. Neurons exposure to Aβ oligomers led to an increase in the number of lysosomes, a decrease in the fraction of moving lysosome and an increase in their size, reminiscent of that found in APP transgenic model of Alzheimer’s disease. We then analyzed the effect of α-syn fibrillar polymorphs, Aβ fibrils, and oligomers on endosomal and lysosomal transport and quantified directed transport of those assemblies within cortical neurons. We report different impacts on endosomal and lysosomal transport parameters and differences in the trajectory lengths of cargoes loaded with pathogenic protein assemblies. Our results suggest that intraneuronal pathogenic protein aggregates internalization and transport may represent a target for novel neuroprotective therapeutic strategies.
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spelling pubmed-91187572022-05-19 Impact of α-Synuclein Fibrillar Strains and β-Amyloid Assemblies on Mouse Cortical Neurons Endo-Lysosomal Logistics Chou, Qiao-Ling Alik, Ania Marquier, François Melki, Ronald Treussart, François Simonneau, Michel eNeuro Research Article: New Research Endosomal transport and positioning cooperate in the establishment of neuronal compartment architecture, dynamics, and function, contributing to neuronal intracellular logistics. Furthermore, dysfunction of endo-lysosomal has been identified as a common mechanism in neurodegenerative diseases. Here, we analyzed endo-lysosomal transport when α-synuclein (α-syn) fibrillar polymorphs, β-amyloid (Aβ) fibrils, and oligomers were externally applied on primary cultures of mouse cortical neurons. To measure this transport, we used a simple readout based on the spontaneous endocytosis in cultured neurons of fluorescent nanodiamonds (FNDs), a perfectly stable nano-emitter, and the subsequent automatic extraction and quantification of their directed motions at high-throughput. α-Syn fibrillar polymorphs, Aβ fibrils, and oligomers induce a 2-fold decrease of the fraction of nanodiamonds transported along microtubules, while only slightly reducing their interaction with cortical neurons. This important decrease in moving endosomes is expected to have a huge impact on neuronal homeostasis. We next assessed lysosomes dynamics, using LysoTracker. Neurons exposure to Aβ oligomers led to an increase in the number of lysosomes, a decrease in the fraction of moving lysosome and an increase in their size, reminiscent of that found in APP transgenic model of Alzheimer’s disease. We then analyzed the effect of α-syn fibrillar polymorphs, Aβ fibrils, and oligomers on endosomal and lysosomal transport and quantified directed transport of those assemblies within cortical neurons. We report different impacts on endosomal and lysosomal transport parameters and differences in the trajectory lengths of cargoes loaded with pathogenic protein assemblies. Our results suggest that intraneuronal pathogenic protein aggregates internalization and transport may represent a target for novel neuroprotective therapeutic strategies. Society for Neuroscience 2022-05-11 /pmc/articles/PMC9118757/ /pubmed/35470226 http://dx.doi.org/10.1523/ENEURO.0227-21.2022 Text en Copyright © 2022 Chou et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article: New Research
Chou, Qiao-Ling
Alik, Ania
Marquier, François
Melki, Ronald
Treussart, François
Simonneau, Michel
Impact of α-Synuclein Fibrillar Strains and β-Amyloid Assemblies on Mouse Cortical Neurons Endo-Lysosomal Logistics
title Impact of α-Synuclein Fibrillar Strains and β-Amyloid Assemblies on Mouse Cortical Neurons Endo-Lysosomal Logistics
title_full Impact of α-Synuclein Fibrillar Strains and β-Amyloid Assemblies on Mouse Cortical Neurons Endo-Lysosomal Logistics
title_fullStr Impact of α-Synuclein Fibrillar Strains and β-Amyloid Assemblies on Mouse Cortical Neurons Endo-Lysosomal Logistics
title_full_unstemmed Impact of α-Synuclein Fibrillar Strains and β-Amyloid Assemblies on Mouse Cortical Neurons Endo-Lysosomal Logistics
title_short Impact of α-Synuclein Fibrillar Strains and β-Amyloid Assemblies on Mouse Cortical Neurons Endo-Lysosomal Logistics
title_sort impact of α-synuclein fibrillar strains and β-amyloid assemblies on mouse cortical neurons endo-lysosomal logistics
topic Research Article: New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118757/
https://www.ncbi.nlm.nih.gov/pubmed/35470226
http://dx.doi.org/10.1523/ENEURO.0227-21.2022
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