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Cited by 154Hereditary Neurological DisordersMetabolism and Genetic DisordersNeurological diseases and metabolism

Loss-or gain-of-function mutations in ACOX1 cause axonal loss via different mechanisms

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Chung, Hyung-lok, Wangler, Michael F., Marcogliese, Paul C., Jo, Juyeon, Ravenscroft, Thomas A., Zuo, Zhongyuan, Duraine, Lita, Sadeghzadeh, Sina +26 more·2020·Neuron
DOI 10.1016/j.neuron.2020.02.021PMC PMC7289150
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Abstract

ACOX1 (acyl-CoA oxidase 1) encodes the first and rate-limiting enzyme of the very-long-chain fatty acid (VLCFA) β-oxidation pathway in peroxisomes and leads to H 2 O 2 production. Unexpectedly, Drosophila (d) ACOX1 is mostly expressed and required in glia, and loss of ACOX1 leads to developmental delay, pupal death, reduced lifespan, impaired synaptic transmission, and glial and axonal loss. Patients who carry a previously unidentified, de novo, dominant variant in ACOX1 (p.N237S) also exhibit glial loss. However, this mutation causes increased levels of ACOX1 protein and function resulting in elevated levels of reactive oxygen species in glia in flies and murine Schwann cells. ACOX1 (p.N237S) patients exhibit a severe loss of Schwann cells and neurons. However, treatment of flies and primary Schwann cells with an antioxidant suppressed the p.N237S-induced neurodegeneration. In summary, both loss and gain of ACOX1 lead to glial and neuronal loss, but different mechanisms are at play and require different treatments.

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  • dACOX1 mutant Drosophila have glial and axonal loss.

    “In contrast, children with ACOX1 deficiency suffer devastating neonatal CNS disease, with VLCFA accumulation and early death [269], and dACOX1 mutant Drosophila have glial and axonal loss [270].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [270]

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Authors
Chung, H.-L., Wangler, M. F., Marcogliese, P. C., Jo, J., Ravenscroft, T. A., Zuo, Z., Duraine, L., Sadeghzadeh, S., Li-Kroeger, D., Schmidt, R. E., Pestronk, A., Rosenfeld, J. A., Burrage, L., Herndon, M. J., Chen, S., Shillington, A., Vawter-Lee, M., Hopkin, R., Rodriguez-Smith, J., Henrickson, M., Lee, B., Moser, A. B., Jones, R. O., Watkins, P., Yoo, T., Mar, S., Choi, M., Bucelli, R. C., Yamamoto, S., Lee, H. K., Prada, C. E., Chae, J.-H., Vogel, T. P., & Bellen, H. J.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Baylor College of Medicine (US)
  • Harvard University (US)
  • Washington University in St. Louis (US)
  • Cincinnati Children's Hospital Medical Center (US)
  • Kennedy Krieger Institute (US)
  • Seoul National University (KR)
  • St. Louis Children's Hospital (US)
Corresponding author
Bellen, Hugo J.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2020-05
Volume
106
Issue
4
Pages
589-606.e6
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2020.02.021
PMC
PMC7289150
OpenAlex
W2980966998
Cited by
154
References
9
Citations by year
2026: 27 · 2025: 29 · 2024: 23 · 2023: 20 · 2022: 20 · 2021: 27 · 2020: 8
FWCI
8.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Multiple Sclerosis Society
  • National Institutes of Health
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords
ACOX1, acyl-CoA oxidase, loss-of-function mutations, gain-of-function mutations, axonal loss, neurodegeneration, reactive oxygen species, Schwann cells, Drosophila, antioxidant treatment, synaptic transmission, lifespan
MeSH terms
Animals, Axons, Drosophila, Humans, Mutation, Nerve Degeneration, Neuroglia, Acyl-CoA Oxidase, Mice, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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