Evidence map›Paper›PMID 40132887›Full record

ArticleLife science alliance2025

Antibodies targeting ADAM17 reverse neurite outgrowth inhibition by myelin-associated inhibitors.

Nayanendu Saha, Eric Chan, Rachelle P Mendoza, Yevgeniy Romin, Murray J Tipping, Dimitar B Nikolov

Abstract read
In one paragraph

Article in Life science alliance, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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.

Nayanendu SahaStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA sahan@mskcc.org.ORCID 0000-0001-8371-9819
Eric ChanMolecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Rachelle P MendozaDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Yevgeniy RominMolecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Murray J TippingMolecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0001-5262-2723
Dimitar B NikolovStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA nikolovd@mskcc.org.ORCID 0000-0001-8774-5061

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Targeting the alpha secretase ADAM10 for the treatment of Alzheimer's diseaseR21AG080685 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI NIKOLOV, DIMITAR B · 2023 to 2024
$487k
NCI NIH HHS P30 CA008748NIA NIH HHS R21 AG080685
6 · The paper itself

Abstract

Upon spinal cord injury, axons attempting to regenerate need to overcome the repulsive actions of myelin-associated inhibitors, including the myelin-associated glycoprotein, Nogo-A, and the oligodendrocyte myelin glycoprotein. These inhibitors bind and signal through a neuronal receptor/co-receptor/transducer complex composed of NgR1, Lingo-1, and p75. Consequently, p75 is cleaved by alpha secretase followed by gamma-secretase, triggering downstream signaling that inhibits axonal regrowth. ADAM10 and ADAM17 are both known to function as alpha secretases in neurons. Here we show that ADAM17, and not ADAM10, is the alpha secretase that recognizes and cleaves p75, when it is a part of a 5-component neuron-myelin signaling complex comprising NgR1, Lingo-1, p75, GT1b, and a myelin inhibitor. Importantly, we demonstrate the ability of inhibitory anti-ADAM17 mAbs to abrogate the cleavage of p75 in a neuroblastoma-glioma cell line and reverse the neurite outgrowth inhibition by myelin-associated inhibitors.

Indexed as

ADAM17 ProteinAntibodies, MonoclonalNeuronal OutgrowthADAM10 ProteinAmyloid Precursor Protein SecretasesAnimalsAxonsCell Line, TumorHumansMembrane ProteinsMiceMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinMyelin ProteinsMyelin SheathNerve Tissue ProteinsADAM10 ProteinADAM17 ProteinADAM17 protein, humanAmyloid Precursor Protein SecretasesAntibodies, MonoclonalMembrane ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinMyelin ProteinsNerve Tissue ProteinsNogo ProteinsNogo Receptor 1Receptor, Nerve Growth Factor

Identifiers

PMID40132887
PMCPMC11938383

What OpenQuestion holds

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LicenceCC BY
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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.