Evidence map›Paper›PMID 40319043›Full record

ArticleNPJ Parkinson's disease2025

Emergent glutamate & dopamine dysfunction in VPS35

A Kamesh, C A Kadgien, N Kuhlmann, S Coady, A Pietrantonio, Y Cousineau, A Khayachi, A Jurado Santos, E P Hurley, J C Barron and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ Parkinson's disease, 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. Vacuolar protein sorting 35 regulates retinal neurovascular functionInternational journal of ophthalmology · 2026
    Article
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

12 authors.

A KameshThe Neuro, McGill University, Montreal, QC, Canada. anusha.kamesh@mail.mcgill.ca.
C A KadgienThe Neuro, McGill University, Montreal, QC, Canada.
N KuhlmannThe Neuro, McGill University, Montreal, QC, Canada.
S CoadyThe Neuro, McGill University, Montreal, QC, Canada.
A PietrantonioThe Neuro, McGill University, Montreal, QC, Canada.
Y CousineauThe Neuro, McGill University, Montreal, QC, Canada.
A KhayachiThe Neuro, McGill University, Montreal, QC, Canada.
A Jurado SantosMedical Research Council Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UK.
E P HurleyDivision of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, NF, Canada.
J C BarronDivision of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, NF, Canada.
M P ParsonsDivision of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, NF, Canada.
A J MilnerwoodThe Neuro, McGill University, Montreal, QC, Canada. austen.milnerwood@mcgill.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The D620N variant in Vacuolar Protein Sorting 35 (VPS35) causes autosomal-dominant, late-onset Parkinson's disease. VPS35 is a core subunit of the retromer complex that canonically recycles transmembrane cargo from sorting endosomes. Although retromer cargoes include many synaptic proteins, VPS35's neuronal functions are poorly understood. To investigate the consequences of the Parkinson's mutation, striatal neurotransmission was assessed in 1- to 6-month-old VPS35 D620N knock-in (VKI) mice. Spontaneous and optogenetically-evoked corticostriatal glutamate transmission was increased in VKI spiny projection neurons by 6 months and was unaffected by acute leucine-rich repeat kinase 2 (LRRK2) inhibition. Total striatal glutamate release by iGluSnFR imaging was similar to wild-type. dLight imaging revealed robust increases in VKI striatal dopamine release by 6 months, which were reversed with acute LRRK2 kinase inhibition. We conclude that increased striatal neurotransmission in VKI mice progressively emerges in young-adulthood, and that dopamine dysfunction is likely the result of sustained, rapidly-reversible, LRRK2 hyperactivity.

Identifiers

PMID40319043
PMCPMC12049453

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.