Evidence map›Paper›PMID 26014385›Full record

ArticleMolecular neurobiology2016

LRRK2 Promotes Tau Accumulation, Aggregation and Release.

Patrícia Silva Guerreiro, Ellen Gerhardt, Tomás Lopes da Fonseca, Mathias Bähr, Tiago Fleming Outeiro, Katrin Eckermann

Open access · greenAbstract read
PubMed 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 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

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  15. Characterization of the activity, aggregation, and toxicity of heterodimers of WT and ALS-associated mutant Sod1.Proceedings of the National Academy of Sciences of the United States of America · 2019
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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 3 institutions in 2 countries.

Patrícia Silva GuerreiroInstituto de Medicina Molecular, 1649-028, Lisbon, Portugal.
Ellen GerhardtDepartment of Neurodegeneration and Restorative Research, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, 37073, Göttingen, Germany.
Tomás Lopes da FonsecaInstituto de Medicina Molecular, 1649-028, Lisbon, Portugal.
Mathias BährDepartment of Neurology, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, 37073, Göttingen, Germany.
Tiago Fleming OuteiroInstituto de Medicina Molecular, 1649-028, Lisbon, Portugal. touteir@gwdg.de.
Katrin EckermannDepartment of Neurology, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, 37073, Göttingen, Germany.
Universitätsmedizin Göttingen · DENanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103 · DENational Legal Medicine Institute · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are known as the most frequent cause of familial Parkinson's disease (PD), but are also present in sporadic cases. The G2019S-LRRK2 mutation is located in the kinase domain of the protein, and has consistently been reported to promote a gain of kinase function. Several proteins have been reported as LRRK2 substrates and/or interactors, suggesting possible pathways involved in neurodegeneration in PD. Hyperphosphorylated Tau protein accumulates in neurofibrillary tangles, a typical pathological hallmark in Alzheimer's disease and frontotemporal dementia. In addition, it is also frequently found in the brains of PD patients. Although LRRK2 is a kinase, it appears that a putative interaction with Tau is phosphorylation-independent. However, the underlying mechanisms and the cellular consequences of this interaction are still unclear. In this study, we demonstrate an interaction between LRRK2 and Tau and that LRRK2 promotes the accumulation of non-monomeric and high-molecular weight (HMW) Tau species independent of its kinase activity. Interestingly, we found that LRRK2 increases Tau secretion, possibly as a consequence of an impairment of Tau proteasomal degradation. Our data highlight a mechanism through which LRRK2 regulates intracellular Tau levels, contributing to the progression of the pathology caused by the LRRK2-mediated proteasome impairment. In total, our findings suggest that the interplay between LRRK2 and proteasome activity might constitute a valid target for therapeutic intervention in PD.

Indexed as

Protein AggregatesAutophagyHEK293 CellsHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Models, BiologicalMolecular WeightProteasome Endopeptidase ComplexProtein BindingProteolysistau ProteinsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Proteasome Endopeptidase ComplexProtein Aggregatestau ProteinsLRRK2Protein accumulationProtein degradationTau

Identifiers

PMID26014385
OpenAlexW418261600

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.