Evidence map›Paper›PMID 40973885›Full record

ArticleActa neuropathologica2025

Alpha synuclein-mediated cytoskeletal dysfunction impairs myelination in human oligodendrocytes.

Jeanette Wihan, Kristina Battis, Alana Hoffmann, Farina Windener, Marcus Himmler, Anish Varghese, Aron Koller, Isabell Karnatz, Dirk W Schubert, Friederike Zunke and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Jeanette WihanDivision of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, 91054, Erlangen, Germany. jeanette.wihan@ibmt.fraunhofer.de.
Kristina BattisDivision of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, 91054, Erlangen, Germany.
Alana HoffmannDivision of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, 91054, Erlangen, Germany.
Farina WindenerInstitute of Neuropathology, University Hospital Münster, 48149, Muenster, Germany.
Marcus HimmlerDepartment of Materials Science and Engineering, Institute of Polymer Materials, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, 91058, Erlangen, Germany.
Anish VargheseDivision of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, 91054, Erlangen, Germany.
Aron KollerDivision of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, 91054, Erlangen, Germany.
Isabell KarnatzProject Center for Stem Cell Process Engineering, Fraunhofer Institute for Biomedical Engineering (IBMT), 97070, Würzburg, Germany.
Dirk W SchubertDepartment of Materials Science and Engineering, Institute of Polymer Materials, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, 91058, Erlangen, Germany.
Friederike ZunkeDivision of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, 91054, Erlangen, Germany.
Wei XiangDivision of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, 91054, Erlangen, Germany.
Tanja KuhlmannInstitute of Neuropathology, University Hospital Münster, 48149, Muenster, Germany.
Jürgen WinklerDivision of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, 91054, Erlangen, Germany. juergen.winkler@uk-erlangen.de.

Funding

Bayerisches Staatsministerium für Bildung und Kultus, Wissenschaft und Kunst Bavarian Research Network "Interaction of Human Brain Cells" (ForInter)Deutsche Forschungsgemeinschaft 270949263/GRK2162
6 · The paper itself

Abstract

Oligodendroglial alpha-synuclein (aSyn) deposits are a key feature in the atypical parkinsonian disorder, multiple system atrophy (MSA) linked to profound myelin loss and neurodegeneration while precise cellular and molecular mechanisms remain unclear. We generated human oligodendrocytes (hOLs) from induced pluripotent stem cells to investigate the impact of aSyn on oligodendroglial morphology, differentiation, and function. We observed an aSyn-induced myelinogenic dysfunction characterized by impaired oligodendroglial process outgrowth, altered cell shape, and increased perinuclear accumulation of the tubulin polymerization promoting protein TPPP/p25α. These changes were associated with a reduced capacity to ensheath axons and were linked to compromised actin remodeling machinery. Actin imbalances were confirmed in post-mortem putaminal tissue from MSA patients. Treatment with a rho-associated protein kinase inhibitor rescued oligodendroglial process formation and improved ensheathment in aSyn-expressing hOLs. Our work emphasizes the aSyn-mediated interference with actin dynamics as a key pathogenic mechanism in MSA, pointing toward a novel therapeutic target for improving myelin maintenance.

Indexed as

alpha-SynucleinCytoskeletonMyelin SheathOligodendrogliaActinsAgedCell DifferentiationCells, CulturedFemaleHumansInduced Pluripotent Stem CellsMaleMiddle AgedMultiple System AtrophyNerve Tissue ProteinsActinsalpha-SynucleinNerve Tissue ProteinsTPPP protein, humanActinAlpha synucleinHuman oligodendrocytesMultiple system atrophyMyelin

Identifiers

PMID40973885
PMCPMC12449394

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.