Evidence map›Paper›PMID 26399642›Full record

ArticleMolecular neurobiology2016

Fibroblast Biomarkers of Sporadic Parkinson's Disease and LRRK2 Kinase Inhibition.

G A Smith, J Jansson, E M Rocha, T Osborn, P J Hallett, O Isacson

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

Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

50 citing papers in PubMed, 66 citations in OpenAlex.

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  13. Molecular mechanisms defining penetrance ofMedizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2022
    Article
  14. Exploring the focal role of LRRK2 kinase in Parkinson's disease.Environmental science and pollution research international · 2022
    Review
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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

6 authors at 2 institutions in 1 country.

G A SmithNeuroregeneration Research Institute, McLean Hospital/ Harvard Medical School, 115 Mill Street, Belmont, 02478, USA.
J JanssonNeuroregeneration Research Institute, McLean Hospital/ Harvard Medical School, 115 Mill Street, Belmont, 02478, USA.
E M RochaNeuroregeneration Research Institute, McLean Hospital/ Harvard Medical School, 115 Mill Street, Belmont, 02478, USA.
T OsbornNeuroregeneration Research Institute, McLean Hospital/ Harvard Medical School, 115 Mill Street, Belmont, 02478, USA.
P J HallettNeuroregeneration Research Institute, McLean Hospital/ Harvard Medical School, 115 Mill Street, Belmont, 02478, USA.
O IsacsonNeuroregeneration Research Institute, McLean Hospital/ Harvard Medical School, 115 Mill Street, Belmont, 02478, USA. isacson@hms.harvard.edu.
McLean Hospital · USHarvard University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

It has been uncertain whether specific disease-relevant biomarker phenotypes can be found using sporadic Parkinson's disease (PD) patient-derived samples, as it has been proposed that there may be a plethora of underlying causes and pathological mechanisms. Fibroblasts derived from familial PD patients harboring leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), and Parkin mutations show clear disease-relevant mitochondrial phenotypes, which are exacerbated under conditions of pharmacological stress. We utilized fibroblasts derived from non-familial sporadic PD patients (without LRRK2 mutations) or LRRK2 mutation carriers to directly compare the cellular phenotypes during and after mitochondrial stress. We then determined the effects of pharmacological LRRK2 kinase inhibition using LRRK2-in-1. We found that there were two distinct populations of sporadic PD patient-derived fibroblast lines. One group of sporadic PD lines was highly susceptible to valinomycin-induced mitochondrial depolarization, emulating the mutant LRRK2 phenotype. These lines showed elevated mitochondrial superoxide/ nitric oxide levels, displayed increased mitochondrial and lysosome co-localization, and an increased rate of mitochondrial collapse, which corresponded with changes in mitochondrial fission and fusion proteins. The application of LRRK2-in-1 reversed decreased levels of mitochondrial and lysosome co-localization and partially restored mitochondrial network associated proteins and the mitochondrial membrane potential in the fibroblasts. This study identifies novel mitochondrial biomarkers in sporadic PD patient-derived fibroblast lines, which could be used as preclinical tools in which to test novel and known neuroprotective compounds.

Indexed as

BenzodiazepinonesBiomarkersCell LineFibroblastsHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LysosomesMembrane Potential, MitochondrialMitochondriaMitochondrial DynamicsParkinson DiseaseProtein KinasesPTEN-Induced Putative KinasePyrimidinesStress, PhysiologicalUbiquitin-Protein LigasesBenzodiazepinonesBiomarkersLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2-IN1parkin proteinProtein KinasesPTEN-Induced Putative KinasePyrimidinesUbiquitin-Protein LigasesValinomycinBiomarkersFibroblastsLRRK2MitochondriaParkinSporadic Parkinson’s disease

Identifiers

PMID26399642
PMCPMC5012155
OpenAlexW2142746955

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.