Evidence map›Paper›PMID 29362387›Full record

ArticleScientific reports2018

Effects of ambroxol on the autophagy-lysosome pathway and mitochondria in primary cortical neurons.

J Magalhaes, M E Gegg, A Migdalska-Richards, A H Schapira

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

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

64 citing papers in PubMed, 92 citations in OpenAlex.

  1. Trial
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  10. Lysosomal storage, impaired autophagy and innate immunity in Gaucher and Parkinson's diseases: insights for drug discovery.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
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  19. PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects,Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  20. Frontiers in molecular neuroscience · 2023
    Review

4 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

4 authors at 1 institution in 1 country.

J MagalhaesDepartment of Clinical Neuroscience, Institute of Neurology, University College London, London, NW3 2PF, UK.
M E GeggDepartment of Clinical Neuroscience, Institute of Neurology, University College London, London, NW3 2PF, UK.ORCID http://orcid.org/0000-0001-8093-0723
A Migdalska-RichardsDepartment of Clinical Neuroscience, Institute of Neurology, University College London, London, NW3 2PF, UK.
A H SchapiraDepartment of Clinical Neuroscience, Institute of Neurology, University College London, London, NW3 2PF, UK. a.schapira@ucl.ac.uk.ORCID http://orcid.org/0000-0002-3018-3966
University College London · GB

Funding

Medical Research Council MR/M006646/1Parkinson's UK G-1104Parkinson's UK K-1507
6 · The paper itself

Abstract

Glucocerebrosidase (GBA1) mutations are the major genetic risk factor for Parkinson's Disease (PD). The pathogenic mechanism is still unclear, but alterations in lysosomal-autophagy processes are implicated due to reduction of mutated glucocerebrosidase (GCase) in lysosomes. Wild-type GCase activity is also decreased in sporadic PD brains. Small molecule chaperones that increase lysosomal GCase activity have potential to be disease-modifying therapies for GBA1-associated and sporadic PD. Therefore we have used mouse cortical neurons to explore the effects of the chaperone ambroxol. This chaperone increased wild-type GCase mRNA, protein levels and activity, as well as increasing other lysosomal enzymes and LIMP2, the GCase transporter. Transcription factor EB (TFEB), the master regulator of the CLEAR pathway involved in lysosomal biogenesis was also increased upon ambroxol treatment. Moreover, we found macroautophagy flux blocked and exocytosis increased in neurons treated with ambroxol. We suggest that ambroxol is blocking autophagy and driving cargo towards the secretory pathway. Mitochondria content was also found to be increased by ambroxol via peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α). Our data suggest that ambroxol, besides being a GCase chaperone, also acts on other pathways, such as mitochondria, lysosomal biogenesis, and the secretory pathway.

Indexed as

AmbroxolAnimalsAutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCerebral CortexExocytosisGene Expression RegulationGene Knockout TechniquesGlucosylceramidaseLysosomesMiceMitochondriaNeuronsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaUp-RegulationAmbroxolBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsGlucosylceramidasePeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mouseTcfeb protein, mouse

Identifiers

PMID29362387
PMCPMC5780491
OpenAlexW2797277973

What OpenQuestion holds

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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.