Evidence map›Paper›PMID 30149180›Full record

ArticleNeurobiology of disease2018

The glycoprotein GPNMB is selectively elevated in the substantia nigra of Parkinson's disease patients and increases after lysosomal stress.

Elizabeth B Moloney, Alyssa Moskites, Eliza J Ferrari, Ole Isacson, Penelope J Hallett

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

Article in Neurobiology of disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
6.6field-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

76 citing papers in PubMed, 124 citations in OpenAlex.

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  19. GPNMB Biomarker Levels in GBA1 Carriers with Lewy Body Disorders.Movement disorders : official journal of the Movement Disorder Society · 2024
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16 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

5 authors at 1 institution in 1 country.

Elizabeth B MoloneyNeuroregeneration Research Institute, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont 02478, USA.
Alyssa MoskitesNeuroregeneration Research Institute, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont 02478, USA.
Eliza J FerrariNeuroregeneration Research Institute, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont 02478, USA.
Ole IsacsonNeuroregeneration Research Institute, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont 02478, USA. Electronic address: isacson@hms.harvard.edu.
Penelope J HallettNeuroregeneration Research Institute, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont 02478, USA. Electronic address: phallett@mclean.harvard.edu.
Harvard University · US

Funding

Prevention of complement and immune-mediated Lewy body dementiaR01AG060195 · NIA · MCLEAN HOSPITAL · PI HALLETT, PENELOPE JANE, HASTINGS, MICHELLE L · 2018 to 2022
$2.9M
Critical analysis of glycosphingolipid pathways in aging and Parkinsons diseaseR01NS092667 · NINDS · MCLEAN HOSPITAL · PI HALLETT, PENELOPE JANE · 2015 to 2018
$1.2M
NIA NIH HHS R01 AG060195NINDS NIH HHS R01 NS092667
6 · The paper itself

Abstract

GPNMB is a glycoprotein observed upon tissue damage and inflammation and is associated with astrocytes, microglia, and macrophages. Gene variations in GPNMB are linked with Parkinson's disease (PD) risk, and changes in protein levels of GPNMB have been found in lysosomal storage disorders, including Gaucher's disease with glucocerebrosidase (GCase) deficiency. In the current study, GPNMB increases were seen in the substantia nigra (SN) of PD patients compared to age-matched controls. Such PD patients have a decrease in GCase activity and corresponding elevation of glycosphingolipids in the SN (Rocha et al., 2015a). Interestingly, transgenic mice modelling synucleinopathy did not show GPNMB elevations or altered GCase activity levels compared to wild-type mice. However, upon CBE-induced GCase lysosomal dysfunction with elevated glycosphingolipids in wild-type mice, there were similar changes in GPNMB levels in the brain as seen in PD patient brains. These results indicate that GPNMB levels do not depend on alpha-synuclein load per se but relate directly to the lipidopathy changes induced by CBE-mediated GCase inhibition. The experimental modelling of elevating glycolipids resulted in GPNMB elevations with glial activation in several brain regions in mice. This is the first demonstration of region-specific elevations of GPNMB protein in Parkinson's disease. The presence of GPNMB in PD patient substantia nigra, the induction of GPNMB after experimental glycosphingolipid increases, but not with pure alpha-synucleinopathy, point towards the potential for primary lipid-induced degeneration in PD.

Indexed as

AgedAged, 80 and overAnimalsCohort StudiesFemaleHumansLysosomesMaleMembrane GlycoproteinsMice, TransgenicMiddle AgedOxidative StressParkinson DiseaseSubstantia NigraGPNMB protein, humanMembrane GlycoproteinsGlucocerebrosidaseGPNMBLipidopathyLysosomeParkinson's diseasePost-mortem

Identifiers

PMID30149180
PMCPMC6748034
OpenAlexW2888541978

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.