Evidence map›Paper›PMID 27482083›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Caspase-1 causes truncation and aggregation of the Parkinson's disease-associated protein α-synuclein.

Wei Wang, Linh T T Nguyen, Christopher Burlak, Fariba Chegini, Feng Guo, Tim Chataway, Shulin Ju, Oriana S Fisher, David W Miller, Debajyoti Datta and 11 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
165citing papers in PubMed, 2 pooled it
16.6field-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

165 citing papers in PubMed, 2 syntheses or guidelines pooled it, 259 citations in OpenAlex.

  1. Pooled it
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  7. ATP13A2 restrains macrophage NLRP3 inflammasome activation to repress neurodegeneration via modulating mitochondrial homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. APurinergic signalling · 2026
    Article
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  19. Innate and adaptive immunity in neurodegenerative disease.Cellular and molecular life sciences : CMLS · 2025
    Review
  20. Article

105 more citing papers are in PubMed but not listed here.

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

21 authors at 9 institutions in 2 countries.

Wei WangDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202;
Linh T T NguyenDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202;
Christopher BurlakSchulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN 55455;
Fariba CheginiDepartment of Human Physiology, Center for Neuroscience, Flinders University, Adelaide 5001, Australia;
Feng GuoDepartment of Human Physiology, Center for Neuroscience, Flinders University, Adelaide 5001, Australia;
Tim ChatawayDepartment of Human Physiology, Center for Neuroscience, Flinders University, Adelaide 5001, Australia;
Shulin JuDepartment of Chemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454; Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454;
Oriana S FisherDepartment of Chemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454; Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454;
David W MillerLaboratory of Neurogenetics, National Institutes of Health, Bethesda, MD 20892;
Debajyoti DattaDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143;
Fang WuDepartment of Chemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454; Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454;
Chun-Xiang WuDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202;
Anuradha LanderuDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202;
James A WellsDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143;
Mark R CooksonLaboratory of Neurogenetics, National Institutes of Health, Bethesda, MD 20892;
Matthew B BoxerChemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892;
Craig J ThomasChemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892;
Wei Ping GaiDepartment of Human Physiology, Center for Neuroscience, Flinders University, Adelaide 5001, Australia;
Dagmar RingeDepartment of Chemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454; Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454; Department of Neurology, Harvard Medical School, Cambridge, MA 02139; Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02116;
Gregory A PetskoDepartment of Chemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454; Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454; Department of Neurology, Harvard Medical School, Cambridge, MA 02139; Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02116; gpetsko@med.cornell.edu qqhoang@iu.edu.
Quyen Q HoangDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202; Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202 gpetsko@med.cornell.edu qqhoang@iu.edu.
Indiana University School of MedicineFlinders University · AUBrandeis University · USNational Center for Advancing Translational Sciences · USNational Institutes of Health · USUniversity of California, San Francisco · USBrigham and Women's Hospital · USHarvard University · USUniversity of Minnesota · US

Funding

Alpha Synuclein, cellular dysfunction and Parkinson diseaseZIAAG000939 · NIA · NATIONAL INSTITUTE ON AGING · PI COOKSON, MARK · 2009 to 2025
$12.7M
Structure and Function of the Parkinson's disease associated protein LRRK2R01GM111639 · NIGMS · INDIANA UNIVERSITY INDIANAPOLIS · PI HOANG, QUYEN QUOC · 2015 to 2019
$1.6M
Structure and conformational dynamics of alpha-synucleinR21NS079881 · NINDS · INDIANA UNIVERSITY INDIANAPOLIS · PI HOANG, QUYEN QUOC · 2012 to 2013
$422k
NIGMS NIH HHS R01 GM111639NINDS NIH HHS R21 NS079881
6 · The paper itself

Abstract

The aggregation of α-synuclein (aSyn) leading to the formation of Lewy bodies is the defining pathological hallmark of Parkinson's disease (PD). Rare familial PD-associated mutations in aSyn render it aggregation-prone; however, PD patients carrying wild type (WT) aSyn also have aggregated aSyn in Lewy bodies. The mechanisms by which WT aSyn aggregates are unclear. Here, we report that inflammation can play a role in causing the aggregation of WT aSyn. We show that activation of the inflammasome with known stimuli results in the aggregation of aSyn in a neuronal cell model of PD. The insoluble aggregates are enriched with truncated aSyn as found in Lewy bodies of the PD brain. Inhibition of the inflammasome enzyme caspase-1 by chemical inhibition or genetic knockdown with shRNA abated aSyn truncation. In vitro characterization confirmed that caspase-1 directly cleaves aSyn, generating a highly aggregation-prone species. The truncation-induced aggregation of aSyn is toxic to neuronal culture, and inhibition of caspase-1 by shRNA or a specific chemical inhibitor improved the survival of a neuronal PD cell model. This study provides a molecular link for the role of inflammation in aSyn aggregation, and perhaps in the pathogenesis of sporadic PD as well.

Indexed as

alpha-SynucleinAlum CompoundsCaspase 1Cell Line, TumorCell SurvivalDipeptidesGene Expression RegulationHumansInflammasomesInterleukin-1betaLewy BodiesLipopolysaccharidesNeuronsNigericinpara-AminobenzoatesProtein Aggregatesalpha-SynucleinAlum Compoundsaluminum sulfatebelnacasanCaspase 1DipeptidesIL1B protein, humanInflammasomesInterleukin-1betaLipopolysaccharidesNigericinpara-AminobenzoatesProtein AggregatesRNA, Small InterferingSNCA protein, humanVitamin K 3aggregationcaspaseinflammasomeParkinson's diseasesynuclein

Identifiers

PMID27482083
PMCPMC5003239
OpenAlexW2503377259

What OpenQuestion holds

Textmetadata
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.