Evidence mapPaperPMID 42454491Full record

ReviewThe Journal of clinical investigation2026

Sterol biosynthesis, brain development, and disease.

Eric S Peeples, Zeljka Korade, Karoly Mirnics

Abstract readReview
In one paragraph

Review in The Journal of clinical investigation, 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.

Eric S PeeplesDepartment of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Zeljka KoradeDepartment of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Karoly MirnicsDepartment of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cholesterol biosynthesis is indispensable for CNS development and function. The developing brain relies almost entirely on intrinsic sterol synthesis to support membrane biogenesis, axonal outgrowth, synaptogenesis, and myelination. Pathogenic variants in sterol biosynthetic enzymes, including DHCR7 and DHCR24, result in complex neurodevelopmental disorders such as Smith-Lemli-Opitz syndrome and desmosterolosis. In addition to cholesterol-lowering drugs (statins), some other pharmacological agents such as antipsychotics, antidepressants, and beta blockers can also inhibit cholesterol biosynthesis due to off-target effects. This inhibition produces dual pathophysiological effects: cholesterol depletion and accumulation of its precursor, 7-dehydrocholesterol, an exceptionally oxidizable molecule that spontaneously generates toxic oxysterols. Given the intense demand for cholesterol synthesis in the developing brain, prenatal exposure to sterol biosynthesis-inhibiting medications may have far-reaching effects. In this Review, we describe convergent biochemical, genetic, and epidemiologic data that implicate developmental sterol dysregulation as a modifiable risk factor for neurodevelopmental pathology and underscore the urgent need for routine sterol pathway safety assessment in drug development and prenatal pharmacotherapy.

Indexed as

BrainCholesterolNeurodevelopmental DisordersSmith-Lemli-Opitz SyndromeSterolsAbnormalities, MultipleAnimalsDehydrocholesterolsFemaleHumansLipid Metabolism, Inborn ErrorsNerve Tissue ProteinsNeurodevelopmentOxidoreductases Acting on CH-CH Group Donors7-dehydrocholesterolCholesterolDehydrocholesterolsDHCR24 protein, humanNerve Tissue ProteinsOxidoreductases Acting on CH-CH Group DonorsSterols

Identifiers

PMID42454491
PMCPMC13367958

What Socratic holds

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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 Socratic graph.