Evidence map›Paper›PMID 34131105›Full record

ArticleCell death & disease2021

RTP801/REDD1 contributes to neuroinflammation severity and memory impairments in Alzheimer's disease.

Leticia Pérez-Sisqués, Anna Sancho-Balsells, Júlia Solana-Balaguer, Genís Campoy-Campos, Marcel Vives-Isern, Ferran Soler-Palazón, Marta Anglada-Huguet, Miguel-Ángel López-Toledano, Eva-Maria Mandelkow, Jordi Alberch and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. 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
3.6field-weighted citation impact, top 6% 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, 44 citations in OpenAlex.

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  4. DDIT3 drives nucleus pulposus cell PANoptosis and intervertebral disc degeneration progression.Apoptosis : an international journal on programmed cell death · 2026
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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

12 authors at 4 institutions in 3 countries.

Leticia Pérez-SisquésDepartament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia, Spain.ORCID http://orcid.org/0000-0002-9682-9811
Anna Sancho-BalsellsDepartament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Júlia Solana-BalaguerDepartament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Genís Campoy-CamposDepartament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Marcel Vives-IsernDepartament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Ferran Soler-PalazónDepartament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Marta Anglada-HuguetGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Miguel-Ángel López-ToledanoNeurelis, Inc., San Diego, CA, USA.
Eva-Maria MandelkowGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Jordi AlberchDepartament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia, Spain.ORCID http://orcid.org/0000-0002-8684-2721
Albert Giralt *Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia, Spain. albertgiralt@ub.edu.ORCID http://orcid.org/0000-0001-5334-0963
Cristina Malagelada *Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia, Spain. cristina.malagelada@ub.edu.ORCID http://orcid.org/0000-0001-7185-436X
Universitat de Barcelona · ESBiomedical Research Networking Center on Neurodegenerative Diseases · ESCenter of Advanced European Studies and Research · DENeurelis (United States) · US

Funding

Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness) RTI2018-094678-A-I00Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness) SAF2014-57160-RMinisterio de Economía y Competitividad (Ministry of Economy and Competitiveness) SAF2017-88812 R
6 · The paper itself

Abstract

RTP801/REDD1 is a stress-regulated protein whose upregulation is necessary and sufficient to trigger neuronal death. Its downregulation in Parkinson's and Huntington's disease models ameliorates the pathological phenotypes. In the context of Alzheimer's disease (AD), the coding gene for RTP801, DDIT4, is responsive to Aβ and modulates its cytotoxicity in vitro. Also, RTP801 mRNA levels are increased in AD patients' lymphocytes. However, the involvement of RTP801 in the pathophysiology of AD has not been yet tested. Here, we demonstrate that RTP801 levels are increased in postmortem hippocampal samples from AD patients. Interestingly, RTP801 protein levels correlated with both Braak and Thal stages of the disease and with GFAP expression. RTP801 levels are also upregulated in hippocampal synaptosomal fractions obtained from murine 5xFAD and rTg4510 mice models of the disease. A local RTP801 knockdown in the 5xFAD hippocampal neurons with shRNA-containing AAV particles ameliorates cognitive deficits in 7-month-old animals. Upon RTP801 silencing in the 5xFAD mice, no major changes were detected in hippocampal synaptic markers or spine density. Importantly, we found an unanticipated recovery of several gliosis hallmarks and inflammasome key proteins upon neuronal RTP801 downregulation in the 5xFAD mice. Altogether our results suggest that RTP801 could be a potential future target for theranostic studies since it could be a biomarker of neuroinflammation and neurotoxicity severity of the disease and, at the same time, a promising therapeutic target in the treatment of AD.

Indexed as

Alzheimer DiseaseAnimalsCase-Control StudiesDisease Models, AnimalEncephalitisFemaleHumansMaleMemory DisordersMiceMice, TransgenicNeuroimmunomodulationNeurotoxicity SyndromesSeverity of Illness IndexTranscription FactorsDDIT4 protein, humanTranscription Factors

Identifiers

PMID34131105
PMCPMC8206344
OpenAlexW3168746894

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.