Parkinson’s disease and multiple system atrophy patient iPSC-derived oligodendrocytes exhibit alpha-synuclein–induced changes in maturation and immune reactive properties

Author:

Azevedo Carla1ORCID,Teku Gabriel2,Pomeshchik Yuriy1ORCID,Reyes Juan F.34ORCID,Chumarina Margarita1,Russ Kaspar1ORCID,Savchenko Ekaterina1ORCID,Hammarberg Anna1ORCID,Lamas Nuno Jorge567ORCID,Collin Anna8,Gouras Gunnar K.9ORCID,Klementieva Oxana10ORCID,Hallbeck Martin3ORCID,Taipa Ricardo11ORCID,Vihinen Mauno2ORCID,Roybon Laurent1

Affiliation:

1. iPSC Laboratory for CNS Disease Modeling, Department of Experimental Medical Science, Lund University, 22184 Lund, Sweden

2. Protein Structure and Bioinformatics, Department of Experimental Medical Science, Lund University, 22184 Lund, Sweden

3. Department of Clinical Pathology, Linköping University, 58185 Linköping, Sweden

4. Department of Biomedical and Clinical Sciences, Linköping University, 58185 Linköping, Sweden

5. Life and Health Sciences Research Institute, School of Medicine, University of Minho, 4710-057 Braga, Portugal

6. Life and Health Sciences Research Institute/3B’s, PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal

7. Anatomic Pathology Service, Pathology Department, Centro Hospitalar e Universitário do Porto, 4099-001 Porto, Portugal

8. Department of Clinical Genetics and Pathology, Region Skåne Office for Medical Services, 22185 Lund, Sweden

9. Experimental Dementia Research Unit, Department of Experimental Medical Science, Lund University, 22184 Lund, Sweden

10. Medical Micro-spectroscopy, Department of Experimental Medical Science, Lund University, 22184 Lund, Sweden

11. Portuguese Brain Bank, Neuropathology Unit, Centro Hospitalar Universitário do Porto, 4099-001 Porto, Portugal

Abstract

Significance Our results demonstrate the existence of early cellular pathways and network alterations in oligodendrocytes in the alpha-synucleinopathies Parkinson’s disease and multiple system atrophy. They further reveal the involvement of an immune component triggered by alpha-synuclein protein, as well as a connection between (epi)genetic changes and immune reactivity in multiple system atrophy. The knowledge generated in this study could be used to devise novel therapeutic approaches to treat synucleinopathies.

Funder

Vetenskapsrådet

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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