Evidence map›Paper›PMID 19815552›Full record

ArticleThe Journal of biological chemistry2009

Low density lipoprotein receptor-related protein 1 promotes anti-apoptotic signaling in neurons by activating Akt survival pathway.

Rodrigo A Fuentealba, Qiang Liu, Takahisa Kanekiyo, Juan Zhang, Guojun Bu

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

63 citing papers in PubMed, 106 citations in OpenAlex.

  1. Review
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  10. Extracellular HSP90α promotes cellular senescence by modulating TGF-β signaling in pulmonary fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  11. Article
  12. Article
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  14. The Multifaceted Role of Plasminogen in Cancer.International journal of molecular sciences · 2021
    Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

3 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Rodrigo A FuentealbaDepartment of Pediatrics, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Qiang Liu
Takahisa Kanekiyo
Juan Zhang
Guojun Bu
Hope Center for Neurological Disorders · US

Funding

TRANSGENIC MOUSE COREP01AG030128 · NIA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI WEEBER, EDWIN JOHN · 2009 to 2013
$9.4M
ApoE Receptor Pathways to Intraneuronal AbetaR01AG027924 · NIA · WASHINGTON UNIVERSITY · PI LI, YONGHE · 2006 to 2021
$3.7M
BRAIN LIPID METABOLISM, DENDRITES AND SYNAPSES IN AGING AND ALZHEIMER'S DISEASER01AG035355 · NIA · MAYO CLINIC JACKSONVILLE · PI BU, GUOJUN · 2010 to 2019
$3.1M
LRP AND APP PROCESSING IN NEURODEGENERATIONR01AG031784 · NIA · WASHINGTON UNIVERSITY · PI BU, GUOJUN · 2008 to 2009
$398k
NIA NIH HHS P01 AG030128NIA NIH HHS R01 AG027924NIA NIH HHS R01 AG031784NIA NIH HHS R01 AG035355
6 · The paper itself

Abstract

The low density lipoprotein receptor-related protein 1 (LRP1) is a multi-ligand receptor abundantly expressed in neurons. Previous work has shown that brain LRP1 levels are decreased during aging and in Alzheimer disease. Although mounting evidence has demonstrated a role for LRP1 in the metabolism of apolipoprotein E/lipoprotein and amyloid-beta peptide, whether LRP1 also plays a direct role in neuronal survival is not clear. Here, we show that LRP1 expression is critical for the survival of primary neurons under stress conditions including trophic withdrawal, the presence of apoptosis inducers, or amyloid-beta-induced neurotoxicity. Using lentiviral short hairpin RNA to knock down endogenous LRP1 expression, we showed that a depletion of LRP1 leads to an activation of caspase-3 and increased neuronal apoptosis, an effect that was rescued by a caspase-3 inhibitor. A correlation between decreased Akt phosphorylation and the activation of caspase-3 was demonstrated in LRP1 knocked down neurons. Notably, LRP1 knockdown decreased insulin receptor levels in primary neurons, suggesting that decreased neuronal survival might be a consequence of an impaired insulin receptor signaling pathway. Correspondingly, both insulin receptor and phospho-Akt levels were decreased in LRP1 forebrain knock-out mice. These results demonstrate that LRP1 mediates anti-apoptotic function in neurons by regulating insulin receptor and the Akt survival pathway and suggest that restoring LRP1 expression in Alzheimer disease brain might be beneficial to inhibiting neurodegeneration.

Indexed as

ApoptosisAmyloid beta-PeptidesAnimalsBrainCaspase 3Cell SurvivalHumansLentivirusLow Density Lipoprotein Receptor-Related Protein-1MiceMice, KnockoutNeurodegenerative DiseasesNeuronsProsencephalonProto-Oncogene Proteins c-aktReceptor, InsulinAmyloid beta-PeptidesCaspase 3Low Density Lipoprotein Receptor-Related Protein-1Proto-Oncogene Proteins c-aktReceptor, Insulin

Identifiers

PMID19815552
PMCPMC2797175
OpenAlexW2112329962

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.