Evidence map›Paper›PMID 34183444›Full record

ArticleLife science alliance2021

Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup.

Francesc X Guix, Ana Marrero Capitán, Álvaro Casadomé-Perales, Irene Palomares-Pérez, Inés López Del Castillo, Verónica Miguel, Leigh Goedeke, Mauricio G Martín, Santiago Lamas, Héctor Peinado and 2 more

Open access · goldAbstract read
In one paragraph

Article in Life science alliance, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.0field-weighted citation impact, top 12% 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

18 citing papers in PubMed, 35 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

12 authors at 4 institutions in 3 countries.

Francesc X GuixMolecular Neuropathology Unit, Physiological and Pathological Processes Program, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid, Spain fguix@cbm.csic.es fguixrafols@gmail.com.ORCID 0000-0001-5781-3799
Ana Marrero CapitánMolecular Neuropathology Unit, Physiological and Pathological Processes Program, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid, Spain.
Álvaro Casadomé-PeralesMolecular Neuropathology Unit, Physiological and Pathological Processes Program, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid, Spain.
Irene Palomares-PérezMolecular Neuropathology Unit, Physiological and Pathological Processes Program, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid, Spain.
Inés López Del CastilloMolecular Neuropathology Unit, Physiological and Pathological Processes Program, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid, Spain.
Verónica MiguelMolecular Pathophysiology of Fibrosis, Physiological and Pathological Processes Program, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid, Spain.
Leigh GoedekeVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA.
Mauricio G MartínInstituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Universidad Nacional de Córdoba (UNC), Córdoba, Argentina.
Santiago LamasMolecular Pathophysiology of Fibrosis, Physiological and Pathological Processes Program, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid, Spain.ORCID 0000-0001-5166-4155
Héctor PeinadoMicroenvironment and Metastasis Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Carlos Fernández-HernandoVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA.
Carlos G DottiMolecular Neuropathology Unit, Physiological and Pathological Processes Program, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid, Spain cdotti@cbm.csic.es.ORCID 0000-0003-4052-1719
Consejo Superior de Investigaciones Científicas · ESYale University · USConsejo Nacional de Investigaciones Científicas y Técnicas · ARSpanish National Cancer Research Centre · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

As neurons age, they show a decrease in their ability to degrade proteins and membranes. Because undegraded material is a source of toxic products, defects in degradation are associated with reduced cell function and survival. However, there are very few dead neurons in the aging brain, suggesting the action of compensatory mechanisms. We show in this work that ageing neurons in culture show large multivesicular bodies (MVBs) filled with intralumenal vesicles (ILVs) and secrete more small extracellular vesicles than younger neurons. We also show that the high number of ILVs is the consequence of the accumulation of cholesterol in MVBs, which in turn is due to decreased levels of the cholesterol extruding protein NPC1. NPC1 down-regulation is the consequence of a combination of upregulation of the NPC1 repressor microRNA 33, and increased degradation, due to Akt-mTOR targeting of NPC1 to the phagosome. Although releasing more exosomes can be beneficial to old neurons, other cells, neighbouring and distant, can be negatively affected by the waste material they contain.

Indexed as

AnimalsCell LineCellular SenescenceCholesterolDown-RegulationExosomesHEK293 CellsHumansMiceMicroRNAsMultivesicular BodiesNeuronsNiemann-Pick C1 ProteinPrimary Cell CultureRatsSignal TransductionCholesterolMicroRNAsMIRN33 microRNA, ratNiemann-Pick C1 ProteinNPC1 protein, rat

Identifiers

PMID34183444
PMCPMC8321659
OpenAlexW3175012470

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.