Evidence map›Paper›PMID 23673310›Full record

ArticleNeurobiology of aging2013

Endolysosome involvement in HIV-1 transactivator protein-induced neuronal amyloid beta production.

Xuesong Chen, Liang Hui, Nicholas H Geiger, Norman J Haughey, Jonathan D Geiger

Abstract read
In one paragraph

Article in Neurobiology of aging, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

59 citing papers in PubMed, 70 citations in OpenAlex.

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  16. HIV-1 Tat endocytosis and retention in endolysosomes affects HIV-1 Tat-induced LTR transactivation in astrocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  17. Endolysosome Localization of ERα Is Involved in the Protective Effect of 17α-Estradiol against HIV-1 gp120-Induced Neuronal Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
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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

5 authors at 2 institutions in 1 country.

Xuesong ChenDepartment of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA. xuesong.chen@med.und.edu
Liang Hui
Nicholas H Geiger
Norman J Haughey
Jonathan D Geiger
University of North Dakota · USJohns Hopkins University · US

Funding

Therapeutic CoreP30MH075673 · NIMH · JOHNS HOPKINS UNIVERSITY · PI Leah Helane Rubin, Barbara Stauch Slusher · 2006 to 2026
$33.2M
TRPC1, CALCIUM AND PARKINSON'S DISEASEP20RR017699 · NCRR · UNIVERSITY OF NORTH DAKOTA · PI GHRIBI, OTHMAN · 2002 to 2011
$19.7M
Pilot Projects CoreP30GM103329 · NIGMS · UNIVERSITY OF NORTH DAKOTA · PI GEIGER, JONATHAN DAVID · 2012 to 2016
$5.1M
The Role of Adenosine in Ketogenic Diet TherapyR01NS065957 · NINDS · TRINITY COLLEGE · PI BOISON, DETLEV, GEIGER, JONATHAN DAVID · 2010 to 2021
$3.9M
HIV Associated CNS Dysfunction with AgingR01AG023471 · NIA · JOHNS HOPKINS UNIVERSITY · PI HAUGHEY, NORMAN J · 2003 to 2007
$1.8M
Perturbation of amyloid processing in HANDR21AG034849 · NIA · JOHNS HOPKINS UNIVERSITY · PI HAUGHEY, NORMAN J · 2010 to 2011
$377k
Neuronal endolysosome involvement in HIV-1 Tat-induced amyloid beta accumulationR21AG043338 · NIA · UNIVERSITY OF NORTH DAKOTA · PI CHEN, XUESONG, GEIGER, JONATHAN DAVID · 2012 to 2013
$336k
NCRR NIH HHS P20RR0017699NCRR NIH HHS P20 RR017699NIA NIH HHS R01 AG023471NIA NIH HHS R21 AG034849NIA NIH HHS R21 AG043338NIA NIH HHS R21AG043338NIGMS NIH HHS P30 GM103329NIGMS NIH HHS P30GM103329NINDS NIH HHS R01 NS065957NINDS NIH HHS R01NS065957
6 · The paper itself

Abstract

The increased life expectancy of people living with HIV-1/AIDS is accompanied by increased prevalence of HIV-1-associated neurocognitive disorder. As well, these individuals are increasingly experiencing Alzheimer's disease (AD)-like neurocognitive problems and neuropathological features such as increased deposition of amyloid beta (Aβ) protein. Findings that Aβ production occurs largely in endolysosomes, that HIV-1 transactivator protein (Tat) disrupts endolysosome function-an early pathological feature of AD-and that HIV-1 Tat can increase Aβ levels prompted us to test the hypothesis that endolysosome dysfunction is associated with HIV-1 Tat-induced increases in neuronal Aβ generation. Using primary cultured rat hippocampal neurons, we found that treatment with HIV-1 Tat caused such morphological changes as enlargement of endolysosomes identified with LysoTracker dye and such functional changes as elevated endolysosome pH measured ratiometrically with LysoSensor dye. The HIV-1 Tat-induced changes in endolysosome function preceded temporally HIV-1 Tat-induced increases in Aβ generation measured using enzyme-linked immunosorbent assay. In addition, we demonstrated that HIV-1 Tat increased endolysosome accumulation of Aβ precursor protein and Aβ identified using immunostaining with 4G8 antibodies. Furthermore, we demonstrated that treatment of neurons with HIV-1 Tat increased endolysosome accumulation of beta amyloid-converting enzyme, the rate-limiting enzymatic step for Aβ production, and enhanced beta amyloid-converting enzyme activity. Together, our findings suggest that HIV-1 Tat increases neuronal Aβ generation and thereby contributes to the development of AD-like pathology in HIV-1-infected individuals by disturbing endolysosome structure and function.

Indexed as

HIV-1AIDS Dementia ComplexAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesCells, CulturedFemaleHippocampusHumansHydrogen-Ion ConcentrationLysosomesNeuronsPregnancyRatsRats, Sprague-DawleyAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBace1 protein, ratrev Gene Products, Human Immunodeficiency VirusAmyloid betaBACE-1EndolysosomeHIV-1 TatpH

Identifiers

PMID23673310
PMCPMC3706576
OpenAlexW2080983287

What OpenQuestion holds

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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 OpenQuestion graph.