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Cited by 12Metabolism and Genetic DisordersLysosomal Storage Disorders ResearchNeurological diseases and metabolism

Pathophysiology of X-Linked Adrenoleukodystrophy: Updates on Molecular Mechanisms

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Parasar, Parveen, Kaur, Navtej, Singh, Jaspreet·2024·Journal of Biotechnology and Biomedicine
DOI 10.26502/jbb.2642-91280151PMC PMC11271253
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Abstract

X-ALD, an inherited monogenic metabolic disorder affecting the CNS and adrenal white matter, is caused by mutations in ABCD1 gene leading to defective fatty acid oxidation in the peroxisomes. This results in accumulation of very long-chain fatty acids, VLCFA, into brain, spinal cord, and body fluids. A single ABCD1mutation does not clearly explain the severity and diverse clinical spectrum of X-ALD phenotypes which suggests that not only genetic but also other modifier genes, epigenetic factors, and environmental factors play a role and contribute to neuroinflammation, mitochondrial dysfunctions, oxidative stress, and metabolic defects seen in phenotypes of ALD. In this review we discuss genotype and phenotype correlation and clinical spectra of X-ALD, previous and recent modifier genetic factors of X-ALD, including novel role of microRNAs (miRNAs) in pathology and as biomarkers. We also discuss the mechanistic interplay of miRNAs and metabolic pathways and potential of targeting miRNAs for X-ALD.

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  • In many neurodegenerative diseases, including AMN, axonal pathology precedes cell body loss in the form of dying back axonopathy.

    “In many neurodegenerative diseases, including AMN [49,89,181,187,288,294,295,296,297], axonal pathology precedes cell body loss in the form of “dying back axonopathy”, in which axons gradually degenerate toward the cell body [298,299].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [296]

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Authors
Parasar, P., Kaur, N., & Singh, J.
Affiliations
Henry Ford Health (US)
Corresponding author
Singh, Jaspreet
ORCID
Venue
Journal of Biotechnology and Biomedicine
Publisher
Fortune Journals
Published
2024
Volume
07
Issue
02
Pages
277-288
ISSN
2642-9128 (ISSN-L)
DOI
10.26502/jbb.2642-91280151
PMC
PMC11271253
OpenAlex
W4399858734
Cited by
12
References
19
Citations by year
2026: 3 · 2025: 7 · 2024: 2
FWCI
3.50
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Biotechnology and Biomedicine (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
Funders
National Institute of Neurological Disorders and Stroke (R01NS114245, R56NS114245, R21NS114775)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords
X-linked adrenoleukodystrophy, ABCD1 gene, peroxisomal fatty acid oxidation, very long chain fatty acids, genetic modifiers, genotype-phenotype correlation, microRNA, biomarkers, neuroinflammation, oxidative stress, mitochondrial dysfunction, peroxisome biogenesis disorders

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