Evidence map›Paper›PMID 36362339›Full record

ArticleInternational journal of molecular sciences2022

New Positive TRPC6 Modulator Penetrates Blood-Brain Barrier, Eliminates Synaptic Deficiency and Restores Memory Deficit in 5xFAD Mice.

Nikita Zernov, Alexander V Veselovsky, Vladimir V Poroikov, Daria Melentieva, Anastasia Bolshakova, Elena Popugaeva

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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. Neuronal Calcium Signaling and Cytoskeletal Dynamics in Neurodegeneration.International journal of molecular sciences · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
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.

Nikita ZernovLaboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, 195251 St. Petersburg, Russia.ORCID 0000-0002-4068-3032
Alexander V VeselovskyDepartment of Bioinformatics, Institute of Biomedical Chemistry, Pogodinskaya St. 10/8, 119121 Moscow, Russia.ORCID 0000-0001-6362-7757
Vladimir V PoroikovDepartment of Bioinformatics, Institute of Biomedical Chemistry, Pogodinskaya St. 10/8, 119121 Moscow, Russia.ORCID 0000-0001-7937-2621
Daria MelentievaLaboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, 195251 St. Petersburg, Russia.
Anastasia BolshakovaLaboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, 195251 St. Petersburg, Russia.
Elena PopugaevaLaboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, 195251 St. Petersburg, Russia.ORCID 0000-0002-6649-0802

Funding

«Best International Grant for PhD» of Peter the Great St. Petersburg Polytechnic University TBAProgram for Basic Research in the Russian Federation for a long-term period (2021-2030) 122030100170-5Russian Science Foundation 20-75-10026
6 · The paper itself

Abstract

Synapse loss in the brain of Alzheimer's disease patients correlates with cognitive dysfunctions. Drugs that limit synaptic loss are promising pharmacological agents. The transient receptor potential cation channel, subfamily C, member 6 (TRPC6) regulates the formation of an excitatory synapse. Positive regulation of TRPC6 results in increased synapse formation and enhances learning and memory in animal models. The novel selective TRPC6 agonist, 3-(3-,4-Dihydro-6,7-dimethoxy-3,3-dimethyl-1-isoquinolinyl)-2H-1-benzopyran-2-one, has recently been identified. Here we present in silico, in vitro, ex vivo, pharmacokinetic and in vivo studies of this compound. We demonstrate that it binds to the extracellular agonist binding site of the human TRPC6, protects hippocampal mushroom spines from amyloid toxicity in vitro, efficiently recovers synaptic plasticity in 5xFAD brain slices, penetrates the blood-brain barrier and recovers cognitive deficits in 5xFAD mice. We suggest that C20 might be recognized as the novel TRPC6-selective drug suitable to treat synaptic deficiency in Alzheimer's disease-affected hippocampal neurons.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBlood-Brain BarrierDisease Models, AnimalHippocampusHumansMemory DisordersMiceMice, TransgenicTRPC6 Cation ChannelAmyloid beta-PeptidesTRPC6 Cation ChannelTRPC6 protein, humanTrpc6 protein, mouseAlzheimer’s diseasebehaviorsynapseTRPC6

Identifiers

PMID36362339
PMCPMC9653995

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.