Evidence map›Paper›PMID 41802147›Full record

ArticleJournal of neuropathology and experimental neurology2026

Azetidine-2-carboxylic acid-induced oligodendrogliopathy in vitro and the pathogenesis of multiple sclerosis.

Raymond A Sobel, Julian R Hinojoza, Muhammad Zoabi

Abstract read
In one paragraph

Article in Journal of neuropathology and experimental neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

3 authors.

Raymond A SobelLaboratory Service, Veterans Affairs Health Care System, Palo Alto, CA, United States.ORCID 0000-0002-0477-9002
Julian R HinojozaLaboratory Service, Veterans Affairs Health Care System, Palo Alto, CA, United States.
Muhammad ZoabiLaboratory Service, Veterans Affairs Health Care System, Palo Alto, CA, United States.

Funding

Stanford University Department of Pathology Gift Fund, Palo Alto Veterans Institute for Research and Boston University Microarray and Sequencing Resource Core Facility
6 · The paper itself

Abstract

Azetidine 2-carboxylic acid (Aze) is consumed by humans and can be misincorporated in place of proline (Pro) in myelin basic protein (MBP). In systemically treated mice Aze induced distinct oligodendroglial (OL) alterations mimicking those in multiple sclerosis (MS) patient normal-appearing white matter. Here, Aze induced an unfolded protein response (UPR), cytoplasmic MBP aggregation, apoptosis and tumor necrosis factor secretion in the human OL lineage MO13.3 cell line. These alterations were counteracted by equimolar Pro suggesting that they are due to Aze substitution for Pro in OL proteins. Gene set enrichment analysis demonstrated extensive Aze-induced alterations of cell cycle, cytoskeletal, organelle, transport, developmental, inflammation-associated and myelination pathways that are altered in OL in MS patients and in toxin and inflammatory MS animal models. These data provide mechanistic support for the hypothesis that Aze protein misincorporation during early life myelinogenesis might over time result in a progressive UPR culminating in a pro-inflammatory/immunomodulatory phenotype, intracytoplasmic MBP aggregation, accelerated senescence and apoptosis in OL. This could occur prior to and independent of an external immune stimulus such as a viral infection. Aze-induced pathological alterations might enhance subsequent antiviral and autoimmune responses and contribute to MS susceptibility, lesion pathogenesis, remyelination failure, neurodegeneration and clinical progression.

Indexed as

Azetidinecarboxylic AcidMultiple SclerosisOligodendrogliaAnimalsApoptosisCell LineHumansMiceMyelin Basic ProteinUnfolded Protein ResponseAzetidinecarboxylic AcidMyelin Basic Proteinapoptosisautoimmunityazetidine 2-carboxylic acidmultiple sclerosismyelin basic proteinoligodendrocyteprolinetumor necrosis factorunfolded protein response

Identifiers

PMID41802147
PMCPMC13293267

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.