Evidence map›Paper›PMID 37454238›Full record

ArticleScientific reports2023

The human acetylcholinesterase C-terminal T30 peptide activates neuronal growth through alpha 7 nicotinic acetylcholine receptors and the mTOR pathway.

Alexandru Graur, Patricia Sinclair, Amanda K Schneeweis, Daniel T Pak, Nadine Kabbani

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.6field-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

15 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
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  8. Review
  9. Article
  10. Oxidative Stress Triggers a Pivotal Peptide Linked to Alzheimer's Disease.International journal of molecular sciences · 2024
    Article
  11. Article
  12. Evidence for a novel neuronal mechanism driving Alzheimer's disease, upstream of amyloid.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Review
  13. Article
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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

5 authors at 3 institutions in 1 country.

Alexandru GraurSchool of Systems Biology, George Mason University, 4400 University Drive, Fairfax, VA, 22030, USA.
Patricia SinclairInterdiscplinary Program in Neuroscience, George Mason University, Fairfax, VA, 22030, USA.
Amanda K SchneeweisDepartment of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC, USA.
Daniel T PakDepartment of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC, USA.
Nadine KabbaniSchool of Systems Biology, George Mason University, 4400 University Drive, Fairfax, VA, 22030, USA. nkabbani@gmu.edu.
George Mason University · USGeorgetown University · USGeorgetown University Medical Center · US

Funding

Aging and Alzheimer's Research Training (AART)T32AG071745 · NIA · GEORGETOWN UNIVERSITY · PI G WILLIAM REBECK · 2021 to 2026
$2.6M
NIA NIH HHS T32 AG071745
6 · The paper itself

Abstract

Acetylcholinesterase (AChE) is a highly conserved enzyme responsible for the regulation of acetylcholine signaling within the brain and periphery. AChE has also been shown to participate in non-enzymatic activity and contribute to cellular development and aging. In particular, enzymatic cleavage of the synaptic AChE isoform, AChE-T, is shown to generate a bioactive T30 peptide that binds to the ⍺7 nicotinic acetylcholine receptor (nAChR) at synapses. Here, we explore intracellular mechanisms of T30 signaling within the human cholinergic neural cell line SH-SY5Y using high performance liquid chromatography (HPLC) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). Proteomic analysis of cells exposed to (100 nM) T30 for 3-days reveals significant changes within proteins important for cell growth. Specifically, bioinformatic analysis identifies proteins that converge onto the mammalian target of rapamycin (mTOR) pathway signaling. Functional experiments confirm that T30 regulates neural cell growth via mTOR signaling and ⍺7 nAChR activation. T30 was found promote mTORC1 pro-growth signaling through an increase in phosphorylated elF4E and S6K1, and a decrease in the autophagy LC3B-II protein. These findings are corroborated in hippocampal neurons and show that T30 promotes dendritic arborization. Taken together, our findings define mTOR as a novel pathway activated by T30 interaction with the nAChR and suggest a role for this process in human disease.

Indexed as

NeuroblastomaReceptors, NicotinicAcetylcholinesteraseC-PeptideHumansPeptidesProteomicsTandem Mass SpectrometryTOR Serine-Threonine KinasesAcetylcholinesteraseC-PeptidePeptidesReceptors, NicotinicTOR Serine-Threonine Kinases

Identifiers

PMID37454238
PMCPMC10349870
OpenAlexW4384407442

What OpenQuestion holds

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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.