Evidence map›Paper›PMID 27518433›Full record

ArticleCell death and differentiation2016

Transthyretin provides trophic support via megalin by promoting neurite outgrowth and neuroprotection in cerebral ischemia.

J R Gomes, R S Nogueira, M Vieira, S D Santos, J P Ferraz-Nogueira, J B Relvas, M J Saraiva

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.0field-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

40 citing papers in PubMed, 76 citations in OpenAlex.

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  18. RNA Targeting and Gene Editing Strategies for Transthyretin Amyloidosis.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023
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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

7 authors at 3 institutions in 2 countries.

J R GomesInstituto de Investigação e Inovação em Saúde (I3S), University of Porto, Porto, Portugal.
R S NogueiraInstituto de Investigação e Inovação em Saúde (I3S), University of Porto, Porto, Portugal.
M VieiraInstituto de Investigação e Inovação em Saúde (I3S), University of Porto, Porto, Portugal.
S D SantosInstituto de Investigação e Inovação em Saúde (I3S), University of Porto, Porto, Portugal.
J P Ferraz-NogueiraInstituto de Investigação e Inovação em Saúde (I3S), University of Porto, Porto, Portugal.
J B RelvasInstituto de Investigação e Inovação em Saúde (I3S), University of Porto, Porto, Portugal.
M J SaraivaInstituto de Investigação e Inovação em Saúde (I3S), University of Porto, Porto, Portugal.
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto · PTInstitut de Biologie Moléculaire et Cellulaire · FRUniversidade do Porto · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Transthyretin (TTR) is a protein whose function has been associated to binding and distribution of thyroid hormones in the body and brain. However, little is known regarding the downstream signaling pathways triggered by wild-type TTR in the CNS either in neuroprotection of cerebral ischemia or in physiological conditions. In this study, we investigated how TTR affects hippocampal neurons in physiologic/pathologic conditions. Recombinant TTR significantly boosted neurite outgrowth in mice hippocampal neurons, both in number and length, independently of its ligands. This TTR neuritogenic activity is mediated by the megalin receptor and is lost in megalin-deficient neurons. We also found that TTR activates the mitogen-activated protein kinase (MAPK) pathways (ERK1/2) and Akt through Src, leading to the phosphorylation of transcription factor CREB. In addition, TTR promoted a transient rise in intracellular calcium through NMDA receptors, in a Src/megalin-dependent manner. Moreover, under excitotoxic conditions, TTR stimulation rescued cell death and neurite loss in TTR KO hippocampal neurons, which are more sensitive to excitotoxic degeneration than WT neurons, in a megalin-dependent manner. CREB was also activated by TTR under excitotoxic conditions, contributing to changes in the balance between Bcl2 protein family members, toward anti-apoptotic proteins (Bcl2/BclXL versus Bax). Finally, we clarify that TTR KO mice subjected to pMCAO have larger infarcts than WT mice, because of TTR and megalin neuronal downregulation. Our results indicate that TTR might be regarded as a neurotrophic factor, because it stimulates neurite outgrowth under physiological conditions, and promotes neuroprotection in ischemic conditions.

Indexed as

Neuronal OutgrowthNeuroprotectionAnimalsApoptosisBrain IschemiaCells, CulturedCell SurvivalHippocampusHumansLow Density Lipoprotein Receptor-Related Protein-2MiceMice, KnockoutNeuronsNeurotoxinsPrealbuminReceptors, N-Methyl-D-AspartateLow Density Lipoprotein Receptor-Related Protein-2NeurotoxinsPrealbuminReceptors, N-Methyl-D-Aspartatesrc-Family Kinases

Identifiers

PMID27518433
PMCPMC5071567
OpenAlexW2513636431

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.