Pathophysiology of X-Linked Adrenoleukodystrophy: Updates on Molecular Mechanisms
Year: 2024
Type: article
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.
Authors: Parveen Parasar, Navtej Kaur, Jaspreet Singh
Institutions: Henry Ford Health, Henry Ford Hospital, Michigan State University
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: diamond
Awards: Use of IPSC to define role of astrocytes in specifying risk for onset of cerebral adrenoleukodystrophy, Use of IPSC to define role of astrocytes in specifying risk for onset of cerebral adrenoleukodystrophy, Deciphering neuroinflammation-specific regulatory RNA and metabolic networks in human iPSC-derived astrocytes in cerebral adrenoleukodystrophy
OpenAlex ID: W4399858734