Evidence map›Paper›PMID 11567048›Full record

Trial reportThe Journal of neuroscience : the official journal of the Society for Neuroscience2001

Familial amyloid polyneuropathy: receptor for advanced glycation end products-dependent triggering of neuronal inflammatory and apoptotic pathways.

M M Sousa, S Du Yan, R Fernandes, A Guimaraes, D Stern, M J Saraiva

Open access · bronzeAbstract readClinical TrialControlled Clinical Trial
PubMed Full text at PMC
In one paragraph

Trial report in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
3.8field-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

60 citing papers in PubMed, 212 citations in OpenAlex.

  1. Mechanisms of damage and therapies for cardiac amyloidosis: a role for inflammation?Clinical research in cardiology : official journal of the German Cardiac Society · 2026
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  16. The role of transthyretin in cell biology: impact on human pathophysiology.Cellular and molecular life sciences : CMLS · 2021
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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

6 authors at 3 institutions in 3 countries.

M M SousaInstitute for Cellular and Molecular Biology, Columbia University, New York, New York 10032, USA.
S Du Yan
R Fernandes
A Guimaraes
D Stern
M J Saraiva
Institut de Biologie Moléculaire et Cellulaire · FRColumbia University · USHospital de Santo António · PT

Funding

STRUCTURAL AND FUNCTIONAL PROPERTIESP01AG017490 · NIA · UNIVERSITY OF KANSAS LAWRENCE · PI LUSTBADER, JOYCE · 2000 to 2010
$16.9M
CORE--NEUROPATHOLOGYP01AG016223 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZLOKOVIC, BERISLAV V · 1999 to 2003
$4.5M
NIA NIH HHS AG16223NIA NIH HHS AG17490NIA NIH HHS P01 AG017490
6 · The paper itself

Abstract

Familial amyloid polyneuropathy (FAP) is a neurodegenerative disorder associated with extracellular deposition of mutant transthyretin (TTR) amyloid fibrils, particularly in the peripheral nervous system. We have hypothesized that binding of TTR fibrils to the receptor for advanced glycation end products (RAGE) on critical cellular targets is associated with a destructive stress response underlying peripheral nerve dysfunction. Analysis of nerve biopsy samples from patients with FAP (n = 16) at different stages of disease (0-3), compared with age-matched controls (n = 4), by semiquantitative immunohistology and in situ hybridization showed increased levels of RAGE, beginning at the earliest stages of the disease (FAP 0; p < 0.02) and especially localized in axons. Upregulation of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-1beta) (approximately threefold; p < 0.02) and the inducible form of nitric oxide synthase (iNOS) ( approximately 2.5-fold; p < 0.04) was also observed in a distribution overlapping RAGE expression. Tyrosine nitration and increased activated caspase-3 in axons from FAP patients (p < 0.03) were apparent. Although these data suggest the presence of ongoing neuronal stress, there was no upregulation of neurotrophins (nerve growth factor and neurotrophin-3) in FAP nerves. Studies on cultured neuronal-like, Schwann, and endothelial cells incubated with TTR fibrils displayed RAGE-dependent expression of cytokines and iNOS at early times (6 and 12 hr, respectively), followed by later (24 hr) activation of caspase-3 and DNA fragmentation. We propose that the interaction of TTR fibrils with RAGE may contribute to cellular stress and toxicity in FAP. Furthermore, there is an apparent lack of responsiveness of Schwann cells in FAP nerve to provide neurotrophic factors.

Indexed as

ApoptosisAdolescentAdultAmyloid NeuropathiesBiopsyCells, CulturedCytokinesHumansInflammationMacromolecular SubstancesMiddle AgedNerve Growth FactorsNeuronsNitric Oxide SynthaseNitric Oxide Synthase Type IIOxidative StressCytokinesMacromolecular SubstancesNerve Growth FactorsNitric Oxide SynthaseNitric Oxide Synthase Type IINOS2 protein, humanPrealbuminReceptor for Advanced Glycation End ProductsReceptors, ImmunologicRNA, Messenger

Identifiers

PMID11567048
PMCPMC6762914
OpenAlexW2129227455

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.