Evidence mapPaperPMID 36966140Full record

ArticleNPJ Parkinson's disease2023

DOPAL initiates αSynuclein-dependent impaired proteostasis and degeneration of neuronal projections in Parkinson's disease.

Anna Masato, Nicoletta Plotegher, Francesca Terrin, Michele Sandre, Gaia Faustini, Andrea Thor, Stephen Adams, Giulia Berti, Susanna Cogo, Federica De Lazzari and 10 more

Open access · goldFull text read
In one paragraph

Article in NPJ Parkinson's disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
7.2field-weighted citation impact, top 2% 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

26 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
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  4. MicroRNAs and synaptic dysfunction in Parkinson's disease.Molecular therapy. Nucleic acids · 2025
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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

20 authors at 5 institutions in 3 countries.

Anna MasatoDepartment of Biology, University of Padova, Padova, 35131, Italy.ORCID http://orcid.org/0000-0003-4450-1838
Nicoletta PlotegherDepartment of Biology, University of Padova, Padova, 35131, Italy.ORCID http://orcid.org/0000-0001-7421-8705
Francesca TerrinDepartment of Biology, University of Padova, Padova, 35131, Italy.ORCID http://orcid.org/0000-0002-3484-1946
Michele SandreDepartment of Neuroscience, University of Padova, Padova, 35131, Italy.
Gaia FaustiniDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, 25123, Italy.ORCID http://orcid.org/0000-0002-0751-3082
Andrea ThorDepartment of Neurosciences, University of California San Diego, La Jolla, CA, 92093-0608, USA.
Stephen AdamsDepartment of Pharmacology, University of California San Diego, La Jolla, CA, 92093-0608, USA.
Giulia BertiDepartment of Biology, University of Padova, Padova, 35131, Italy.
Susanna CogoDepartment of Biology, University of Padova, Padova, 35131, Italy.
Federica De LazzariDepartment of Biology, University of Padova, Padova, 35131, Italy.ORCID http://orcid.org/0000-0003-4676-8851
Camilla Maria FontanaDepartment of Biology, University of Padova, Padova, 35131, Italy.ORCID http://orcid.org/0000-0001-7520-0814
Paul Anthony MartinezDepartment of Pharmacology and Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Randy StrongDepartment of Pharmacology and Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.ORCID http://orcid.org/0000-0001-6643-3288
Rina BandopadhyayReta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology, London, WC1N 1PJ, UK.
Marco BisagliaDepartment of Biology, University of Padova, Padova, 35131, Italy.ORCID http://orcid.org/0000-0002-3968-8418
Arianna BellucciDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, 25123, Italy.ORCID http://orcid.org/0000-0002-9581-1919
Elisa GreggioDepartment of Biology, University of Padova, Padova, 35131, Italy.ORCID http://orcid.org/0000-0002-8172-3598
Luisa Dalla ValleDepartment of Biology, University of Padova, Padova, 35131, Italy.ORCID http://orcid.org/0000-0001-8097-6369
Daniela BoassaDepartment of Neurosciences, University of California San Diego, La Jolla, CA, 92093-0608, USA. dboassa@ucsd.edu.
Luigi BubaccoDepartment of Biology, University of Padova, Padova, 35131, Italy. luigi.bubacco@unipd.it.ORCID http://orcid.org/0000-0001-7927-9208
University of Padua · ITUniversity of California San Diego · USThe University of Texas Health Science Center at San Antonio · USUniversity of Brescia · ITNational Hospital for Neurology and Neurosurgery · GB

Funding

IVEM and Image Analysis ResourceP41GM103412 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELLISMAN, MARK H · 2012 to 2019
$17.9M
New Probe and Methods for Correlated LM & EMR01GM086197 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ADAMS, STEPHEN ROY, BOASSA, DANIELA · 2008 to 2020
$8.3M
Detoxification of Biogenic Aldehydes in Parkinson's DiseaseI01BX001641 · VA · SOUTH TEXAS VETERANS HEALTH CARE SYSTEM · PI STRONG, RANDY · 2013 to 2023
BLRD Research Career Scientist Award ApplicationIK6BX006289 · VA · SOUTH TEXAS VETERANS HEALTH CARE SYSTEM · PI RANDY STRONG · 2023 to 2026
BLRD VA I01 BX001641BLRD VA IK6 BX006289NIGMS NIH HHS P41 GM103412NIGMS NIH HHS R01 GM086197
6 · The paper itself

Abstract

Dopamine dyshomeostasis has been acknowledged among the determinants of nigrostriatal neuron degeneration in Parkinson's disease (PD). Several studies in experimental models and postmortem PD patients underlined increasing levels of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL has been shown to covalently modify the presynaptic protein αSynuclein (αSyn), whose misfolding and aggregation represent a major trait of PD pathology, triggering αSyn oligomerization in dopaminergic neurons. Here, we demonstrated that DOPAL elicits αSyn accumulation and hampers αSyn clearance in primary neurons. DOPAL-induced αSyn buildup lessens neuronal resilience, compromises synaptic integrity, and overwhelms protein quality control pathways in neurites. The progressive decline of neuronal homeostasis further leads to dopaminergic neuron loss and motor impairment, as showed in in vivo models. Finally, we developed a specific antibody which detected increased DOPAL-modified αSyn in human striatal tissues from idiopathic PD patients, corroborating the translational relevance of αSyn-DOPAL interplay in PD neurodegeneration.

Identifiers

PMID36966140
PMCPMC10039907
OpenAlexW4360949472

What Socratic holds

Textfull text, public
LicenceCC BY
measurements read196
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.