Evidence map›Paper›PMID 30352158›Full record

ArticleACS chemical neuroscience2019

Role of Parkinson's Disease-Linked Mutations and N-Terminal Acetylation on the Oligomerization of α-Synuclein Induced by 3,4-Dihydroxyphenylacetaldehyde.

Vanderlei de Araújo Lima, Lucas Alex do Nascimento, David Eliezer, Cristian Follmer

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS chemical neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

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3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 40 citations in OpenAlex.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

4 authors at 2 institutions in 2 countries.

Vanderlei de Araújo LimaDepartment of Physical Chemistry, Institute of Chemistry , Federal University of Rio de Janeiro , Rio de Janeiro 21941-909 , Brazil.
Lucas Alex do NascimentoDepartment of Physical Chemistry, Institute of Chemistry , Federal University of Rio de Janeiro , Rio de Janeiro 21941-909 , Brazil.
David EliezerDepartment of Biochemistry, Weill Cornell Medical College , Cornell University , New York , New York 10065 , United States.
Cristian FollmerDepartment of Physical Chemistry, Institute of Chemistry , Federal University of Rio de Janeiro , Rio de Janeiro 21941-909 , Brazil.ORCID 0000-0001-6178-0432
Universidade Federal do Rio de Janeiro · BRCornell University · US

Funding

Structure and Function of Alpha-SynucleinR37AG019391 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI ELIEZER, DAVID · 2010 to 2019
$3.4M
NIA NIH HHS R37 AG019391
6 · The paper itself

Abstract

Identifying the mechanisms by which the presynaptic protein α-synuclein (aSyn) is associated with neurodegeneration of dopamine neurons is a major priority in the Parkinson's disease (PD) field. Studies indicate that DOPAL (3,4-dihydroxyphenylacetaldehyde), an aldehyde generated from the enzymatic oxidation of dopamine, may convert aSyn monomer into a neurotoxin via formation of covalently stabilized toxic oligomers. Herein we investigated the role of N-terminal acetylation and familial aSyn mutations (A30P, A53T, E46K, G51D, and H50Q) on DOPAL-induced oligomerization of the protein. Our results indicate that the wild-type (WT) N-terminally acetylated aSyn (Ac-aSyn) is less prone to form oligomers upon incubation with DOPAL than the non-N-terminally acetylated protein. On the other hand, familial mutants from Ac-aSyn, particularly A53T, E46K, and H50Q increased the formation of DOPAL-derived aSyn oligomers, especially large oligomers. Binding of aSyn to synaptic-like small unilamellar vesicles (SUVs) protected distinctive aSyn variants against the effects of DOPAL. While N-terminal acetylation increased the protective action of SUVs against DOPAL-induced aSyn oligomerization, A53T, A30P, and H50Q mutations in Ac-aSyn had an opposite effect. This means that PD-linked mutations may not only perturb the affinity of aSyn for membranes but also influence the formation of DOPAL-mediated oligomers. Overall, our findings provide important evidence for the existence of a connection between familial mutations of aSyn, their distinct affinity to lipid membranes, and the formation of potentially toxic oligomers of the protein mediated by DOPAL.

Indexed as

3,4-Dihydroxyphenylacetic AcidAcetylationalpha-SynucleinDopamineDopaminergic NeuronsHumansMembrane LipidsMutationOxidation-ReductionParkinson DiseaseProtein MultimerizationProtein Processing, Post-Translational3,4-dihydroxyphenylacetaldehyde3,4-Dihydroxyphenylacetic Acidalpha-SynucleinDopamineMembrane Lipidsalpha-synucleinDOPALfamilial mutationslipid vesiclesN-terminal acetylationoligomers

Identifiers

PMID30352158
PMCPMC6467814
OpenAlexW2898517063

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Registered trials

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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.