System-based integrated metabolomics and microRNA analysis identifies potential molecular alterations in human X-linked cerebral adrenoleukodystrophy brain
Recommended Citation
Poisson LM, Kaur N, Felicella MM, and Singh J. System-based integrated metabolomics and microRNA analysis identifies potential molecular alterations in human X-linked cerebral Adrenoleukodystrophy brain. Hum Mol Genet 2023.
Document Type
Article
Publication Date
11-17-2023
Publication Title
Human molecular genetics
Abstract
X-linked adrenoleukodystrophy is a severe demyelinating neurodegenerative disease mainly affecting males. The severe cerebral adrenoleukodystrophy (cALD) phenotype has a poor prognosis and underlying mechanism of onset and progression of neuropathology remains poorly understood. In this study we aim to integrate metabolomic and microRNA (miRNA) datasets to identify variances associated with cALD. Postmortem brain tissue samples from five healthy controls (CTL) and five cALD patients were utilized in this study. White matter from ALD patients was obtained from normal-appearing areas, away from lesions (NLA) and from the periphery of lesions- plaque shadow (PLS). Metabolomics was performed by gas chromatography coupled with time-of-flight mass spectrometry and miRNA expression analysis was performed by next generation sequencing (RNAseq). Principal component analysis revealed that among the three sample groups (CTL, NLA and PLS) there were 19 miRNA, including several novel miRNA, of which 17 were increased with disease severity and 2 were decreased. Untargeted metabolomics revealed 13 metabolites with disease severity-related patterns with 7 increased and 6 decreased with disease severity. Ingenuity pathway analysis of differentially altered metabolites and miRNA comparing CTL with NLA and NLA with PLS, identified several hubs of metabolite and signaling molecules and their upstream regulation by miRNA. The transomic approach to map the crosstalk between miRNA and metabolomics suggests involvement of specific molecular and metabolic pathways in cALD and offers opportunity to understand the complex underlying mechanism of disease severity in cALD.
Medical Subject Headings
Male; Humans; Adrenoleukodystrophy; MicroRNAs; Neurodegenerative Diseases; Brain; Phenotype; Metabolomics
PubMed ID
37656183
Volume
32
Issue
23
First Page
3249
Last Page
3262
