Evidence map›Paper›PMID 31664682›Full record

ArticleNeuromolecular medicine2020

Identification of PP2A and S6 Kinase as Modifiers of Leucine-Rich Repeat Kinase-Induced Neurotoxicity.

Joan Poh Ling Sim, Wang Ziyin, Adeline Henry Basil, Shuping Lin, Zhongcan Chen, Chengwu Zhang, Li Zeng, Yu Cai, Kah-Leong Lim

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

Article in Neuromolecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. G3 (Bethesda, Md.) · 2020
    Article
  4. Review
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

9 authors at 3 institutions in 2 countries.

Joan Poh Ling SimNeurodegeneration Research Laboratory, National Neuroscience Institute, 11, Jalan Tan Tock Seng, Singapore, 308433, Singapore.
Wang ZiyinNeurodegeneration Research Laboratory, National Neuroscience Institute, 11, Jalan Tan Tock Seng, Singapore, 308433, Singapore.
Adeline Henry BasilNeurodegeneration Research Laboratory, National Neuroscience Institute, 11, Jalan Tan Tock Seng, Singapore, 308433, Singapore.
Shuping LinNeurodegeneration Research Laboratory, National Neuroscience Institute, 11, Jalan Tan Tock Seng, Singapore, 308433, Singapore.
Zhongcan ChenNeural Stem Cell Research Laboratory, National Neuroscience Institute, Singapore, Singapore.
Chengwu ZhangNeurodegeneration Research Laboratory, National Neuroscience Institute, 11, Jalan Tan Tock Seng, Singapore, 308433, Singapore.
Li ZengNeural Stem Cell Research Laboratory, National Neuroscience Institute, Singapore, Singapore.
Yu CaiTemasek Life Science Laboratories, Singapore, Singapore.
Kah-Leong LimNeurodegeneration Research Laboratory, National Neuroscience Institute, 11, Jalan Tan Tock Seng, Singapore, 308433, Singapore. kah_leong_lim@nni.com.sg.
National Neuroscience Institute · SGNanjing Tech University · CNTemasek Life Sciences Laboratory · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mutations in LRRK2 are currently recognized as the most common monogenetic cause of Parkinsonism. The elevation of kinase activity of LRRK2 that frequently accompanies its mutations is widely thought to contribute to its toxicity. Accordingly, many groups have developed LRRK2-specific kinase inhibitors as a potential therapeutic strategy. Given that protein phosphorylation is a reversible event, we sought to elucidate the phosphatase(s) that can reverse LRRK2-mediated phosphorylation, with the view that targeting this phosphatase(s) may similarly be beneficial. Using an unbiased RNAi phosphatase screen conducted in a Drosophila LRRK2 model, we identified PP2A as a genetic modulator of LRRK2-induced neurotoxicity. Further, we also identified ribosomal S6 kinase (S6K), a target of PP2A, as a novel regulator of LRRK2 function. Finally, we showed that modulation of PP2A or S6K activities ameliorates LRRK2-associated disease phenotype in Drosophila.

Indexed as

AnimalsAnimals, Genetically ModifiedCell LineCeramidesDisease Models, AnimalDrosophila melanogasterDrosophila ProteinsDrug Evaluation, PreclinicalEnzyme ActivationFingolimod HydrochlorideGain of Function MutationGene Knockdown TechniquesLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MiceMice, Inbred C57BLMice, TransgenicCeramidesDrosophila ProteinsFingolimod HydrochlorideLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Lrrk2 protein, mouseLRRK protein, Drosophilamts protein, DrosophilaPhosphoprotein PhosphatasesProtein Phosphatase 2Protein Serine-Threonine KinasesRecombinant ProteinsRibosomal Protein S6 KinasesRibosomal Protein S6 Kinases, 90-kDaRNA, Small InterferingRps6ka1 protein, mousetws protein, DrosophilaWdb protein, DrosophilaWrd protein, DrosophilaDrosophilaLRRK2MitochondriaNeuroprotectionParkinson’s disease

Identifiers

PMID31664682
PMCPMC7230064
OpenAlexW2982293408

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.