Evidence map›Paper›PMID 41467187›Full record

ArticleiScience2025

Targeting Cdc42 improves motor phenotype in Parkinson's disease mice and reveals age-dependent susceptibility to α-synuclein.

Verena Bopp, Jaehyun LeeBae, Patrick Oeckl, Julia K Kühlwein, Veselin Grozdanov, Martin Kiechle, Benjamin Mayer, Bettina Möhrle, Hartmut Geiger, Karin M Danzer

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Verena BoppDepartment of Neurology, University Clinic Ulm, 89081 Ulm, Germany.
Jaehyun LeeBaeDepartment of Neurology, University Clinic Ulm, 89081 Ulm, Germany.
Patrick OecklDepartment of Neurology, University Clinic Ulm, 89081 Ulm, Germany.
Julia K KühlweinDepartment of Neurology, University Clinic Ulm, 89081 Ulm, Germany.
Veselin GrozdanovDepartment of Neurology, University Clinic Ulm, 89081 Ulm, Germany.
Martin KiechleDepartment of Neurology, University Clinic Ulm, 89081 Ulm, Germany.
Benjamin MayerInstitute of Epidemiology and Medical Biometry, Ulm University, 89075 Ulm, Germany.
Bettina MöhrleInstitute of Molecular Medicine, Ulm University, 89081 Ulm, Germany.
Hartmut GeigerInstitute of Molecular Medicine, Ulm University, 89081 Ulm, Germany.
Karin M DanzerDepartment of Neurology, University Clinic Ulm, 89081 Ulm, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aging and accumulation of α-synuclein (α-syn) oligomers in the brain are indisputably linked to Parkinson's disease (PD). Using an inducible α-syn oligomer mouse model, we demonstrate that the induction of PD-associated α-syn oligomers for the same time span caused PD-associated symptoms only in aged, but not in young mice. Biochemical studies revealed that α-syn oligomer formation precedes motor decline, with age and α-syn expression jointly determining the motor phenotype. Single-nucleus RNA sequencing (snRNA-seq) identified a PD-related transcriptional signature in basal ganglia neurons (BGNs), which overlapped in part with aging-associated changes. Short-term pharmacological inhibition of the small RhoGTPase CDC42 in aged, symptomatic animals improved motor function without reducing oligomer levels. These findings indicate that aging processes strongly influence the susceptibility to PD-like symptoms and that targeting age-related pathways, rather than α-syn oligomer burden alone, may provide effective strategies to improve outcomes in PD.

Indexed as

Model organismMolecular biologyNeuroscienceTranscriptomics

Identifiers

PMID41467187
PMCPMC12744266

What OpenQuestion 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 OpenQuestion graph.