Evidence map›Paper›PMID 34024778›Full record

ArticleJournal of Parkinson's disease2021

Neuroprotective Potential of a Small Molecule RET Agonist in Cultured Dopamine Neurons and Hemiparkinsonian Rats.

Juho-Matti Renko, Arun Kumar Mahato, Tanel Visnapuu, Konsta Valkonen, Mati Karelson, Merja H Voutilainen, Mart Saarma, Raimo K Tuominen, Yulia A Sidorova

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

Article in Journal of Parkinson's disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% 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

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

  1. Pooled it
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  9. Biological ActivityBiomacromolecules · 2023
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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

9 authors at 2 institutions in 2 countries.

Juho-Matti RenkoDivision of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Arun Kumar MahatoInstitute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.
Tanel VisnapuuDivision of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Konsta ValkonenDivision of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Mati KarelsonInstitute of Chemistry, University of Tartu, Tartu, Estonia.
Merja H VoutilainenDivision of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Mart SaarmaInstitute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.
Raimo K TuominenDivision of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Yulia A SidorovaInstitute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.
University of Helsinki · FIUniversity of Tartu · EE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundParkinson's disease (PD) is a progressive neurological disorder where loss of dopamine neurons in the substantia nigra and dopamine depletion in the striatum cause characteristic motor symptoms. Currently, no treatment is able to halt the progression of PD. Glial cell line-derived neurotrophic factor (GDNF) rescues degenerating dopamine neurons both in vitro and in animal models of PD. When tested in PD patients, however, the outcomes from intracranial GDNF infusion paradigms have been inconclusive, mainly due to poor pharmacokinetic properties.

objectiveWe have developed drug-like small molecules, named BT compounds that activate signaling through GDNF's receptor, the transmembrane receptor tyrosine kinase RET, both in vitro and in vivo and are able to penetrate through the blood-brain barrier. Here we evaluated the properties of BT44, a second generation RET agonist, in immortalized cells, dopamine neurons and rat 6-hydroxydopamine model of PD.

methodsWe used biochemical, immunohistochemical and behavioral methods to evaluate the effects of BT44 on dopamine system in vitro and in vivo.

resultsBT44 selectively activated RET and intracellular pro-survival AKT and MAPK signaling pathways in immortalized cells. In primary midbrain dopamine neurons cultured in serum-deprived conditions, BT44 promoted the survival of the neurons derived from wild-type, but not from RET knockout mice. BT44 also protected cultured wild-type dopamine neurons from MPP+-induced toxicity. In a rat 6-hydroxydopamine model of PD, BT44 reduced motor imbalance and seemed to protect dopaminergic fibers in the striatum.

conclusionBT44 holds potential for further development into a novel, possibly disease-modifying, therapy for PD.

Indexed as

Neuroprotective AgentsParkinson DiseaseAnimalsDopamineDopaminergic NeuronsGlial Cell Line-Derived Neurotrophic FactorHumansMiceOxidopamineProto-Oncogene Proteins c-retRatsSubstantia NigraDopamineGlial Cell Line-Derived Neurotrophic FactorNeuroprotective AgentsOxidopamineProto-Oncogene Proteins c-retRET protein, humanRet protein, ratAKT pathwayBT44glial cell line-derived neurotrophic factorMAPK pathwayneuroprotectionParkinson’s diseaserat 6-hydroxydopamine (6-OHDA) modelreceptor tyrosine kinase RETRET agonist

Identifiers

PMID34024778
PMCPMC8461720
OpenAlexW3162716554

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.