Evidence map›Paper›PMID 25925093›Full record

ArticleJournal of neurovirology2015

Herpes simplex virus type 1 infection in neurons leads to production and nuclear localization of APP intracellular domain (AICD): implications for Alzheimer's disease pathogenesis.

Livia Civitelli, Maria Elena Marcocci, Ignacio Celestino, Roberto Piacentini, Enrico Garaci, Claudio Grassi, Giovanna De Chiara, Anna Teresa Palamara

Abstract read
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In one paragraph

Article in Journal of neurovirology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

28 citing papers in PubMed, 49 citations in OpenAlex.

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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

8 authors at 5 institutions in 1 country.

Livia CivitelliDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy. livia.civitelli@liu.se.
Maria Elena MarcocciDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
Ignacio CelestinoDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
Roberto PiacentiniInstitute of Human Physiology, Università Cattolica del Sacro Cuore, Rome, Italy.
Enrico GaraciIRCCS San Raffaele Pisana, Telematic University, Rome, Italy.
Claudio GrassiInstitute of Human Physiology, Università Cattolica del Sacro Cuore, Rome, Italy.
Giovanna De ChiaraInstitute of Translational Pharmacology, CNR, Rome, Italy.
Anna Teresa PalamaraDepartment of Public Health and Infectious Diseases, Institute Pasteur Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy.
Sapienza University of Rome · ITUniversità Cattolica del Sacro Cuore · ITIstituto di Farmacologia Traslazionale · ITIstituto di Ricovero e Cura a Carattere Scientifico San RaffaeleIstituto Pasteur · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Several data indicate that neuronal infection with herpes simplex virus type 1 (HSV-1) causes biochemical alterations reminiscent of Alzheimer's disease (AD) phenotype. They include accumulation of amyloid-β (Aβ), which originates from the cleavage of amyloid precursor protein (APP), and hyperphosphorylation of tau protein, which leads to neurofibrillary tangle deposition. HSV-1 infection triggers APP processing and drives the production of several fragments including APP intracellular domain (AICD) that exerts transactivating properties. Herein, we analyzed the production and intracellular localization of AICD following HSV-1 infection in neurons. We also checked whether AICD induced the transcription of two target genes, neprilysin (nep) and glycogen synthase kinase 3β (gsk3β), whose products play a role in Aβ clearance and tau phosphorylation, respectively. Our data indicate that HSV-1 led to the accumulation and nuclear translocation of AICD in neurons. Moreover, results from chromatin immunoprecipitation assay showed that AICD binds the promoter region of both nep and gsk3β. Time course analysis of NEP and GSK3β expression at both mRNA and protein levels demonstrated that they are differently modulated during infection. NEP expression and enzymatic activity were initially stimulated but, with the progression of infection, they were down-regulated. In contrast, GSK3β expression remained nearly unchanged, but the analysis of its phosphorylation suggests that it was inactivated only at later stages of HSV-1 infection. Thus, our data demonstrate that HSV-1 infection induces early upstream events in the cell that may eventually lead to Aβ deposition and tau hyperphosphorylation and further suggest HSV-1 as a possible risk factor for AD.

Indexed as

Alzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsBlotting, WesternCells, CulturedCerebral CortexChromatin ImmunoprecipitationGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHerpes SimplexHerpesvirus 1, HumanImmunohistochemistryImmunoprecipitationNeprilysinNeuronsRatsAmyloid beta-Protein PrecursorGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGSK3B protein, humanGsk3b protein, ratNeprilysinAICDAlzheimer’s diseaseAPPGSK3βHerpes simplex virus (HSV-1)NeprilysinNeurodegeneration

Identifiers

PMID25925093
OpenAlexW2160294319

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.