Evidence map›Paper›PMID 39635117›Full record

ArticleiScience2024

Hyperactivation of Hedgehog signaling impedes myelin development and repair via cholesterol dysregulation in oligodendrocytes.

Minxi Fang, Xuan Wang, Lixia Chen, Fang Li, Sitong Wang, Leyi Shen, Huanyi Yang, Lifen Sun, Xue Wang, Junlin Yang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2024. 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. Review
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

12 authors.

Minxi FangCollege of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Xuan WangCollege of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Lixia ChenZhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.
Fang LiZhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.
Sitong WangZhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.
Leyi ShenZhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.
Huanyi YangZhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.
Lifen SunZhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.
Xue WangZhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.
Junlin YangZhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.
Mengsheng QiuCollege of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Xiaofeng XuZhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The failure to remyelinate demyelinated axons poses a significant challenge in the treatment of multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. Here, we investigated the role of Hedgehog (Hh) signaling in myelin formation during development and under pathological conditions. Using conditional gain-of-function analyses, we found that hyperactivation of Hh signaling in oligodendrocyte precursor cells (OPCs) inhibits oligodendrocyte (OL) differentiation and myelination. Notably, sustained activation of Hh signaling in adult OPCs hinders myelin repair following LPC-induced focal demyelination. Through RNA sequencing, we discovered that genes associated with cholesterol synthesis were upregulated, and observed intracellular cholesterol accumulation in Hh-activated OPCs. Importantly, pharmacological stimulation of cholesterol transport was able to rescue the OL differentiation and myelination defects in mice. These findings establish a functional connection between Hh signaling, cholesterol homeostasis, and remyelination, providing insights for the strategic design of employing Hh signaling modulators in treating demyelinating neurodegenerative diseases.

Indexed as

Cell biologyDevelopmental biologyPathophysiology

Identifiers

PMID39635117
PMCPMC11615242

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.