Evidence map›Paper›PMID 36920906›Full record

ArticleCell reports2023

Dopamine transporter and synaptic vesicle sorting defects underlie auxilin-associated Parkinson's disease.

D J Vidyadhara, Mahalakshmi Somayaji, Nigel Wade, Betül Yücel, Helen Zhao, N Shashaank, Joseph Ribaudo, Jyoti Gupta, TuKiet T Lam, Dalibor Sames and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
10.9field-weighted citation impact, top 1% of its field
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

42 citing papers in PubMed, 57 citations in OpenAlex.

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  11. Roles in physiology and disease of the inositol phosphatase synaptojanin 1.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026
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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 at 5 institutions in 1 country.

D J VidyadharaDepartment of Neurology, Yale University, New Haven, CT, USA; Department of Neuroscience, Yale University, New Haven, CT, USA.
Mahalakshmi SomayajiDepartment of Psychiatry, Columbia University, New York, NY, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA.
Nigel WadeDepartment of Neurology, Yale University, New Haven, CT, USA; Department of Neuroscience, Yale University, New Haven, CT, USA.
Betül YücelDepartment of Neurology, Yale University, New Haven, CT, USA; Department of Neuroscience, Yale University, New Haven, CT, USA.
Helen ZhaoDepartment of Neurology, Yale University, New Haven, CT, USA.
N ShashaankDivision of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA; Department of Computer Science, Columbia University, New York, NY, USA; New York Genome Center, New York, NY, USA.
Joseph RibaudoDepartment of Neurology, Yale University, New Haven, CT, USA.
Jyoti GuptaDepartment of Neuroscience, Yale University, New Haven, CT, USA.
TuKiet T LamKeck MS and Proteomics Resource, Departments of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Dalibor SamesDepartment of Chemistry and NeuroTechnology Center, Columbia University, New York, NY, USA.
Lois E GreeneLaboratory of Cell Biology, NHLBI, National Institutes of Health, Bethesda, MD, USA.
David L SulzerDepartment of Psychiatry, Columbia University, New York, NY, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA; Departments of Neurology and Pharmacology, Columbia University, New York, NY, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.
Sreeganga S ChandraDepartment of Neurology, Yale University, New Haven, CT, USA; Department of Neuroscience, Yale University, New Haven, CT, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University, New Haven, CT, USA. Electronic address: sreeganga.chandra@yale.edu.
Yale University · USColumbia University · USNational Heart Lung and Blood Institute · USNew York Genome Center · USResearch Network (United States) · US

Funding

Yale/NIDA Neuroproteomics Research CenterP30DA018343 · NIDA · YALE UNIVERSITY · PI ANGUS C. NAIRN, Kenneth Robert WILLIAMS · 2004 to 2026
$37.1M
The Dopamine Synapse and Associative LearningR01DA007418 · NIDA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI David Sulzer · 1999 to 2026
$9.4M
Development of Fluorescent False NeurotransmittersR01MH108186 · NIMH · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI SAMES, DALIBOR, SULZER, DAVID · 2015 to 2024
$5.8M
Yale Macaque Brain ResourceR01MH113257 · NIMH · YALE UNIVERSITY · PI Alvaro Duque · 2017 to 2026
$4.3M
Autoimmune Features of Neurodegenerative DisordersR01NS095435 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SETTE, ALESSANDRO, SULZER, DAVID · 2018 to 2022
$4.2M
Role of Glucosylsphingosine in Parkinson Disease and Dementia with Lewy BodiesRF1NS110354 · NINDS · YALE UNIVERSITY · PI CHANDRA, SREEGANGA S · 2019 to 2022
$2.5M
Chemical Targeting of Sensors and Pharmacological Probes in the BrainR01MH122470 · NIMH · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI SAMES, DALIBOR, SULZER, DAVID · 2020 to 2023
$2.3M
Investigating the Functions of RME8 in Parkinson's DiseaseR21NS132546 · NINDS · YALE UNIVERSITY · PI CHANDRA, SREEGANGA S · 2023 to 2024
$461k
NIDA NIH HHS P30 DA018343NIDA NIH HHS R01 DA007418NIMH NIH HHS R01 MH108186NIMH NIH HHS R01 MH113257NIMH NIH HHS R01 MH122470NINDS NIH HHS R01 NS095435NINDS NIH HHS R21 NS132546NINDS NIH HHS RF1 NS110354
6 · The paper itself

Abstract

Auxilin participates in the uncoating of clathrin-coated vesicles (CCVs), thereby facilitating synaptic vesicle (SV) regeneration at presynaptic sites. Auxilin (DNAJC6/PARK19) loss-of-function mutations cause early-onset Parkinson's disease (PD). Here, we utilized auxilin knockout (KO) mice to elucidate the mechanisms through which auxilin deficiency and clathrin-uncoating deficits lead to PD. Auxilin KO mice display cardinal features of PD, including progressive motor deficits, α-synuclein pathology, nigral dopaminergic loss, and neuroinflammation. Significantly, treatment with L-DOPA ameliorated motor deficits. Unbiased proteomic and neurochemical analyses of auxilin KO brains indicated dopamine dyshomeostasis. We validated these findings by demonstrating slower dopamine reuptake kinetics in vivo, an effect associated with dopamine transporter misrouting into axonal membrane deformities in the dorsal striatum. Defective SV protein sorting and elevated synaptic autophagy also contribute to ineffective dopamine sequestration and compartmentalization, ultimately leading to neurodegeneration. This study provides insights into how presynaptic endocytosis deficits lead to dopaminergic vulnerability and pathogenesis of PD.

Indexed as

Parkinson DiseaseAnimalsAuxilinsDopamineDopamine Plasma Membrane Transport ProteinsMiceProtein TransportProteomicsSubstantia NigraSynaptic VesiclesAuxilinsDopamineDopamine Plasma Membrane Transport Proteinsaxonal deformityclathrin-coated vesiclesclathrin-mediated endocytosisCP: Neurosciencedopaminedorsal striatumendolysosomal systemL-DOPALewy bodiessubstantia nigrasynaptic autophagy∝-synuclein

Identifiers

PMID36920906
PMCPMC10127800
OpenAlexW4324145225

What OpenQuestion holds

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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.