What the study found
The study found that neuronal cells exposed to alpha-synuclein (a protein that can form aggregates) have impaired lysosomal degradation and autophagic flux, which reduces their ability to clear these aggregates. It also found that this impaired clearance can increase transfer of alpha-synuclein from neurons to microglia, specialized brain immune cells, through tunneling nanotubes.
Why the authors say this matters
The authors conclude that dysfunctional autophagy in neurons may drive the outsourcing of alpha-synuclein aggregates to microglia. The findings indicate that differences in lysosomal handling between neurons and microglia may help explain how these aggregates are redistributed between the two cell types.
What the researchers tested
The researchers used human neuronal and microglial cell lines, and they also examined human iPSC-derived neurons and microglia (cells made from induced pluripotent stem cells). They assessed lysosomal turnover, lysophagy, autophagic flux, aggregate clearance, and transfer of alpha-synuclein through tunneling nanotubes.
What worked and what didn't
Microglia showed higher lysosomal turnover, particularly through lysophagy, and were able to degrade transferred aggregates efficiently. Neuronal lysosomes showed compromised degradative capacity and impaired autophagic flux after alpha-synuclein exposure, and inhibiting autophagy further enhanced tunneling nanotube-mediated transfer from neurons to microglia.
What to keep in mind
The abstract describes work in cell lines and human iPSC-derived cells, so the findings are limited to the systems studied there. No other limitations are described in the available summary.
Key points
- Neuronal cells exposed to alpha-synuclein showed reduced lysosomal degradation and impaired autophagic flux.
- Microglia had higher lysosomal turnover, especially through lysophagy.
- Autophagy inhibition increased tunneling nanotube-mediated transfer of alpha-synuclein from neurons to microglia.
- Microglia co-cultured with alpha-synuclein-containing neurons upregulated autophagy flux and degraded transferred aggregates efficiently.
- The same response to alpha-synuclein aggregates was reported in human iPSC-derived neurons and microglia.
Disclosure
- Research title:
- Neuronal autophagy impairment promotes alpha-synuclein transfer to microglia
- Authors:
- Ranabir Chakraborty, Francesca Palese, Philippa Samella, Veronica Testa, Jara Montero-Muñoz, Sylvie Syan, Takashi Nonaka, Masato Hasegawa, Antonella Consiglio, Chiara Zurzolo
- Institutions:
- Centre National de la Recherche Scientifique, Centre National de la Recherche Scientifique, Centre National de la Recherche Scientifique, Centre National de la Recherche Scientifique, Centre National de la Recherche Scientifique, Federico II University Hospital, Institut d'Investigació Biomédica de Bellvitge, Institut d'Investigació Biomédica de Bellvitge, Institut d'Investigació Biomédica de Bellvitge, Institut Pasteur, Institut Pasteur, Institut Pasteur, Institut Pasteur, Institut Pasteur, Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Institute of Medical Science, Université Paris Cité, Université Paris Cité, Université Paris Cité, Université Paris Cité, Université Paris Cité, Université Paris-Saclay, University of Cambridge, University of Naples Federico II
- Publication date:
- 2026-03-12
- OpenAlex record:
- View
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