Cited by 360Neuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and TreatmentsAlzheimer's disease research and treatments

Microglia jointly degrade fibrillar alpha-synuclein cargo by distribution through tunneling nanotubes

Open access
Scheiblich, Hannah, Dansokho, Cira, Mercan, Dilek, Schmidt, Susanne V., Bousset, Luc, Wischhof, Lena, Eikens, Frederik, Odainic, Alexandru +7 more·2021·Cell

Abstract

Microglia are the CNS resident immune cells that react to misfolded proteins through pattern recognition receptor ligation and activation of inflammatory pathways. Here, we studied how microglia handle and cope with α-synuclein (α-syn) fibrils and their clearance. We found that microglia exposed to α-syn establish a cellular network through the formation of F-actin-dependent intercellular connections, which transfer α-syn from overloaded microglia to neighboring naive microglia where the α-syn cargo got rapidly and effectively degraded. Lowering the α-syn burden attenuated the inflammatory profile of microglia and improved their survival. This degradation strategy was compromised in cells carrying the LRRK2 G2019S mutation. We confirmed the intercellular transfer of α-syn assemblies in microglia using organotypic slice cultures, 2-photon microscopy, and neuropathology of patients. Together, these data identify a mechanism by which microglia create an "on-demand" functional network in order to improve pathogenic α-syn clearance.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cell.2021.09.007

Cites

74 of 74 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Scheiblich, H., Dansokho, C., Mercan, D., Schmidt, S. V., Bousset, L., Wischhof, L., Eikens, F., Odainic, A., Spitzer, J., Griep, A., Schwartz, S., Bano, D., Latz, E., Melki, R., & Heneka, M. T.
Affiliations
  • University of Bonn (DE)
  • Centre National de la Recherche Scientifique (FR)
  • German Center for Neurodegenerative Diseases (DE)
Corresponding author
Heneka, Michael T.
Venue
Cell
Publisher
Elsevier BV
Published
2021-09
Volume
184
Issue
20
Pages
5089-5106.e21
ISSN
0092-8674 (ISSN-L)
OpenAlex
W3199862549
Cited by
360
References
74
Citations by year
2026: 59 · 2025: 84 · 2024: 76 · 2023: 67 · 2022: 68 · 2021: 5
FWCI
21.62
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Open Repository and Bibliography (University of Luxembourg) (submittedVersion, other-oa)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion, cc-by)
  • HAL (submittedVersion, cc-by)
  • DZNE Pub (submittedVersion, cc-by)
Funders
  • EU Joint Programme – Neurodegenerative Disease Research
  • Agence Nationale de la Recherche (ANR-11-INBS-0011)
  • National Institute on Aging (R01AG059752)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
microglia, alpha-synuclein, tunneling nanotubes, intercellular transfer, LRRK2 G2019S mutation, microglial inflammation, microglial survival, neurodegeneration, organotypic slice cultures
MeSH terms
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Actins, Aged, Aged, 80 and over, Animals, Cytoskeleton, Female, Humans, Inflammation, Male, Mice, Inbred C57BL, Mitochondria, Down-Regulation, Apoptosis, Reactive Oxygen Species, Microglia, Cell Membrane Structures, Nanotubes, Mice, alpha-Synuclein, Transcriptome, Proteolysis, Protein Aggregates

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review