Evidence map›Paper›PMID 39201779›Full record

ArticleInternational journal of molecular sciences2024

Inhibition of Calcineurin with FK506 Reduces Tau Levels and Attenuates Synaptic Impairment Driven by Tau Oligomers in the Hippocampus of Male Mouse Models.

Michela Marcatti, Batbayar Tumurbaatar, Michela Borghi, Jutatip Guptarak, Wen-Ru Zhang, Balaji Krishnan, Rakez Kayed, Anna Fracassi, Giulio Taglialatela

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. Exploring the PLD1-tau interaction in Frontotemporal Dementia.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  9. 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

9 authors.

Michela MarcattiMitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA.
Batbayar TumurbaatarMitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA.
Michela BorghiMitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA.
Jutatip GuptarakMitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA.
Wen-Ru ZhangMitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA.
Balaji KrishnanMitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA.ORCID 0000-0003-2074-4165
Rakez KayedMitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA.
Anna FracassiMitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA.
Giulio TaglialatelaMitchell Center for Neurodegenerative Disease, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA.ORCID 0000-0003-4795-447X

Funding

Tau oligomer conformers and synaptic vulnerability/resilience in AD and related disordersR01AG073133 · NIA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI LIMON, AGENOR, TAGLIALATELA, GIULIO · 2021 to 2025
$3.8M
Calcineurin Mediates the Synergistic Toxicity of Tau and Aβ OligomersRF1AG060718 · NIA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI KAYED, RAKEZ, TAGLIALATELA, GIULIO · 2019 to 2019
$3.5M
Role of microglia in cognitive resilience to ADR21AG082230 · NIA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI FRACASSI, ANNA · 2023 to 2024
$440k
Calcineurin Mediates the Synergistic Toxicity of Tau and Aβ OligomersR01AG060718 · NIA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI KAYED, RAKEZ, TAGLIALATELA, GIULIO · 2019 to 2019
$39k
Alzheimer's Association AARF22973974NIA NIH HHS R01 AG060718NIA NIH HHS R01 AG073133NIA NIH HHS R21 AG082230NIA NIH HHS RF1 AG060718NIH HHS AG060718NIH HHS AG073133NIH HHS AG082230
6 · The paper itself

Abstract

Alzheimer's disease (AD) is the most common age-associated neurodegenerative disorder, characterized by progressive cognitive decline, memory impairment, and structural brain changes, primarily involving Aβ plaques and neurofibrillary tangles of hyperphosphorylated tau protein. Recent research highlights the significance of smaller Aβ and Tau oligomeric aggregates (AβO and TauO, respectively) in synaptic dysfunction and disease progression. Calcineurin (CaN), a key calcium/calmodulin-dependent player in regulating synaptic function in the central nervous system (CNS) is implicated in mediating detrimental effects of AβO on synapses and memory function in AD. This study aims to investigate the specific impact of CaN on both exogenous and endogenous TauO through the acute and chronic inhibition of CaN. We previously demonstrated the protective effect against AD of the immunosuppressant CaN inhibitor, FK506, but its influence on TauO remains unclear. In this study, we explored the short-term effects of acute CaN inhibition on TauO phosphorylation and TauO-induced memory deficits and synaptic dysfunction. Mice received FK506 post-TauO intracerebroventricular injection and TauO levels and phosphorylation were assessed, examining their impact on CaN and GSK-3β. The study investigated FK506 preventive/reversal effects on TauO-induced clustering of CaN and GSK-3β. Memory and synaptic function in TauO-injected mice were evaluated with/without FK506. Chronic FK506 treatment in 3xTgAD mice explored its influence on CaN, Aβ, and Tau levels. This study underscores the significant influence of CaN inhibition on TauO and associated AD pathology, suggesting therapeutic potential in targeting CaN for addressing various aspects of AD onset and progression. These findings provide valuable insights for potential interventions in AD, emphasizing the need for further exploration of CaN-targeted strategies.

Indexed as

CalcineurinCalcineurin InhibitorsDisease Models, AnimalHippocampusSynapsesTacrolimustau ProteinsAlzheimer DiseaseAnimalsGlycogen Synthase Kinase 3 betaMaleMicePhosphorylationCalcineurinCalcineurin InhibitorsGlycogen Synthase Kinase 3 betaTacrolimustau ProteinsAlzheimer’s diseasecalcineurinFK506oligomersTau

Identifiers

PMID39201779
PMCPMC11354963

What Socratic holds

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LicenceCC BY
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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 Socratic graph.