Evidence map›Paper›PMID 31312839›Full record

ArticleBrain : a journal of neurology2019

Arylsulfatase A, a genetic modifier of Parkinson's disease, is an α-synuclein chaperone.

Jun Sung Lee, Kazuaki Kanai, Mari Suzuki, Woojin S Kim, Han Soo Yoo, YuHong Fu, Dong-Kyu Kim, Byung Chul Jung, Minsun Choi, Kyu Won Oh and 18 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 2 pooled it
4.7field-weighted citation impact, top 4% 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

33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.

  1. Pooled it
  2. Association of Rare Variants in ARSA with Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2023
    Pooled it
  3. Article
  4. Sphingolipidoses: expanding the spectrum of α-synucleinopathies.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Neurology. Genetics · 2025
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Association of rare variants inmedRxiv : the preprint server for health sciences · 2023
    Article
  16. Review
  17. Review
  18. Plasma arylsulfatase A levels are associated with cognitive function in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 6 institutions in 3 countries.

Jun Sung LeeDepartment of Biomedical Sciences, Neuroscience Research Institute, and Department of Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kazuaki KanaiDepartment of Neurology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
Mari SuzukiDiabetic Neuropathy Project, Department of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
Woojin S KimBrain and Mind Centre, Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia.
Han Soo YooDepartment of Neurology, Yonsei University College of Medicine, Seoul, Korea.
YuHong FuBrain and Mind Centre, Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia.
Dong-Kyu KimDepartment of Biomedical Sciences, Neuroscience Research Institute, and Department of Medicine, Seoul National University College of Medicine, Seoul, Korea.
Byung Chul JungDepartment of Biomedical Sciences, Neuroscience Research Institute, and Department of Medicine, Seoul National University College of Medicine, Seoul, Korea.
Minsun ChoiDepartment of Biomedical Sciences, Neuroscience Research Institute, and Department of Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kyu Won OhDepartment of Biomedical Sciences, Neuroscience Research Institute, and Department of Medicine, Seoul National University College of Medicine, Seoul, Korea.
Yuanzhe LiDepartment of Neurology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
Mitsuyoshi NakataniDepartment of Neurology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
Tomoko NakazatoDepartment of Neurology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
Satoko SekimotoDepartment of Neurology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
Manabu FunayamaDepartment of Neurology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
Hiroyo YoshinoDepartment of Neurology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
Shin-Ichiro KuboDepartment of Neurology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
Kenya NishiokaDepartment of Neurology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
Ryusuke SakaiDepartment of Neurotherapeutics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Morio UeyamaDepartment of Neurotherapeutics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Hideki MochizukiDepartment of Neurology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
He-Jin LeeDepartmen of Anatomy, School of Medicine, Konkuk University, Seoul, Korea.
Sergio Pablo SardiGenzyme, a Sanofi Company, Framingham, Massachusetts, USA.
Glenda M HallidayBrain and Mind Centre, Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia.
Yoshitaka NagaiDepartment of Neurotherapeutics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Phil Hyu LeeDepartment of Neurology, Yonsei University College of Medicine, Seoul, Korea.
Nobutaka HattoriDepartment of Neurology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
Seung-Jae LeeDepartment of Biomedical Sciences, Neuroscience Research Institute, and Department of Medicine, Seoul National University College of Medicine, Seoul, Korea.
Juntendo University · JPSeoul National University · KROsaka University · JPUniversity of Sydney · AUYonsei University · KRKonkuk University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mutations in lysosomal genes increase the risk of neurodegenerative diseases, as is the case for Parkinson's disease. Here, we found that pathogenic and protective mutations in arylsulfatase A (ARSA), a gene responsible for metachromatic leukodystrophy, a lysosomal storage disorder, are linked to Parkinson's disease. Plasma ARSA protein levels were changed in Parkinson's disease patients. ARSA deficiency caused increases in α-synuclein aggregation and secretion, and increases in α-synuclein propagation in cells and nematodes. Despite being a lysosomal protein, ARSA directly interacts with α-synuclein in the cytosol. The interaction was more extensive with protective ARSA variant and less with pathogenic ARSA variant than wild-type. ARSA inhibited the in vitro fibrillation of α-synuclein in a dose-dependent manner. Ectopic expression of ARSA reversed the α-synuclein phenotypes in both cell and fly models of synucleinopathy, the effects correlating with the extent of the physical interaction between these molecules. Collectively, these results suggest that ARSA is a genetic modifier of Parkinson's disease pathogenesis, acting as a molecular chaperone for α-synuclein.

Indexed as

Mutation, MissensePoint MutationAdultAgedalpha-SynucleinAnimalsAnimals, Genetically ModifiedBrainCaenorhabditis elegansCaenorhabditis elegans ProteinsCells, CulturedCerebroside-SulfataseDementiaDrosophila melanogasterDrosophila ProteinsFemalealpha-SynucleinCaenorhabditis elegans ProteinsCerebroside-SulfataseDrosophila ProteinsMolecular ChaperonesRecombinant Proteinsarylsulfatase Amolecular chaperoneParkinson’s diseaseprotein aggregation and propagationα-synuclein

Identifiers

PMID31312839
OpenAlexW2956819816

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.