Evidence map›Paper›PMID 30696719›Full record

ArticleMolecular pharmacology2019

Derivatives of Piperazines as Potential Therapeutic Agents for Alzheimer's Disease.

Elena Popugaeva, Daria Chernyuk, Hua Zhang, Tatyana Y Postnikova, Karina Pats, Elena Fedorova, Vladimir Poroikov, Aleksey V Zaitsev, Ilya Bezprozvanny

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

Article in Molecular pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.3field-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

20 citing papers in PubMed, 36 citations in OpenAlex.

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  14. Sulfur-containing therapeutics in the treatment of Alzheimer's disease.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021
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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 3 institutions in 2 countries.

Elena PopugaevaLaboratory of Molecular Neurodegeneration, Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russian Federation (E.P., D.C., I.B.); Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (H.Z., I.B.); Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russian Federation (T.Y.P., A.V.Z.); VVS Laboratory Inc., Ulica Dostoevskogo 44, St. Petersburg, Russian Federation (K.P., E.F.); Institute of Biomedical Chemistry, Moscow, Russian Federation (V.P.).
Daria ChernyukLaboratory of Molecular Neurodegeneration, Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russian Federation (E.P., D.C., I.B.); Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (H.Z., I.B.); Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russian Federation (T.Y.P., A.V.Z.); VVS Laboratory Inc., Ulica Dostoevskogo 44, St. Petersburg, Russian Federation (K.P., E.F.); Institute of Biomedical Chemistry, Moscow, Russian Federation (V.P.).
Hua ZhangLaboratory of Molecular Neurodegeneration, Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russian Federation (E.P., D.C., I.B.); Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (H.Z., I.B.); Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russian Federation (T.Y.P., A.V.Z.); VVS Laboratory Inc., Ulica Dostoevskogo 44, St. Petersburg, Russian Federation (K.P., E.F.); Institute of Biomedical Chemistry, Moscow, Russian Federation (V.P.).
Tatyana Y PostnikovaLaboratory of Molecular Neurodegeneration, Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russian Federation (E.P., D.C., I.B.); Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (H.Z., I.B.); Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russian Federation (T.Y.P., A.V.Z.); VVS Laboratory Inc., Ulica Dostoevskogo 44, St. Petersburg, Russian Federation (K.P., E.F.); Institute of Biomedical Chemistry, Moscow, Russian Federation (V.P.).
Karina PatsLaboratory of Molecular Neurodegeneration, Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russian Federation (E.P., D.C., I.B.); Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (H.Z., I.B.); Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russian Federation (T.Y.P., A.V.Z.); VVS Laboratory Inc., Ulica Dostoevskogo 44, St. Petersburg, Russian Federation (K.P., E.F.); Institute of Biomedical Chemistry, Moscow, Russian Federation (V.P.).
Elena FedorovaLaboratory of Molecular Neurodegeneration, Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russian Federation (E.P., D.C., I.B.); Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (H.Z., I.B.); Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russian Federation (T.Y.P., A.V.Z.); VVS Laboratory Inc., Ulica Dostoevskogo 44, St. Petersburg, Russian Federation (K.P., E.F.); Institute of Biomedical Chemistry, Moscow, Russian Federation (V.P.).
Vladimir PoroikovLaboratory of Molecular Neurodegeneration, Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russian Federation (E.P., D.C., I.B.); Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (H.Z., I.B.); Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russian Federation (T.Y.P., A.V.Z.); VVS Laboratory Inc., Ulica Dostoevskogo 44, St. Petersburg, Russian Federation (K.P., E.F.); Institute of Biomedical Chemistry, Moscow, Russian Federation (V.P.).
Aleksey V ZaitsevLaboratory of Molecular Neurodegeneration, Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russian Federation (E.P., D.C., I.B.); Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (H.Z., I.B.); Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russian Federation (T.Y.P., A.V.Z.); VVS Laboratory Inc., Ulica Dostoevskogo 44, St. Petersburg, Russian Federation (K.P., E.F.); Institute of Biomedical Chemistry, Moscow, Russian Federation (V.P.).
Ilya BezprozvannyLaboratory of Molecular Neurodegeneration, Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russian Federation (E.P., D.C., I.B.); Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (H.Z., I.B.); Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russian Federation (T.Y.P., A.V.Z.); VVS Laboratory Inc., Ulica Dostoevskogo 44, St. Petersburg, Russian Federation (K.P., E.F.); Institute of Biomedical Chemistry, Moscow, Russian Federation (V.P.) Ilya.Bezprozvanny@UTSouthwestern.edu.
Institute of Biomedical Chemistry · RUPeter the Great St. Petersburg Polytechnic University · RUThe University of Texas Southwestern Medical Center · US

Funding

Calcium signaling and synaptic maintenance in Alzheimers diseaseRF1AG055577 · NIA · UT SOUTHWESTERN MEDICAL CENTER · PI BEZPROZVANNY, ILYA B, KAVALALI, EGE T · 2017 to 2017
$3.0M
Presenilins and neuronal calcium dyshomeostasisR01NS080152 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI BEZPROZVANNY, ILYA B · 2013 to 2017
$2.3M
NIA NIH HHS RF1 AG055577NINDS NIH HHS R01 NS080152
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that is the major cause of dementia in the elderly. There is no cure against AD. We have recently discovered a novel transient receptor potential canonical 6 (TRPC6)-mediated intracellular signaling pathway that regulates the stability of dendritic spines and plays a role in memory formation. We have previously shown that TRPC6 agonists exert beneficial effects in models of AD and may serve as lead compounds for development of AD therapeutic agents. In the current study, we used the Clarivate Analytics Integrity database to search for additional TRPC6 agonists. We selected four compounds to study as potential neuroprotective agents. We applied bioinformatics analyses to test the basic pharmacological properties of the selected compounds. We performed in vitro screening of these compounds to validate their ability to protect mushroom spines from amyloid toxicity and determined that two of these compounds exert neuroprotective effects in the nanomolar concentration range. We have chosen one of these compounds [piperazine (PPZ)] for further testing. In agreement with previously published data, we have shown that PPZ potentiates TRPC6 channels. We demonstrated that the neuroprotective mechanism of the investigated PPZ is based on activation of neuronal store-operated calcium entry in spines. We have shown that PPZ restores long-term potentiation induction in 6-month-old 5xFAD mouse hippocampal slices. The obtained results suggest that PPZ and its derivatives are potential lead molecules for development of AD therapeutic agents.

Indexed as

Alzheimer DiseaseAnimalsCalcium SignalingDendritic SpinesDisease Models, AnimalHippocampusLong-Term PotentiationMiceMice, Inbred C57BLNeuronsNeuroprotective AgentsPiperazinesTRPC Cation ChannelsNeuroprotective AgentsPiperazinesTRPC Cation Channels

Identifiers

PMID30696719
PMCPMC6402417
OpenAlexW2912393050

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.