• ABCD1 gene
• X‐linked adrenoleukodystrophy
• astrocytes
• human‐induced pluripotent stem cells
• lipid homeostasis
• peroxisome

• Humans
• Adrenoleukodystrophy/metabolism
• Adrenoleukodystrophy/pathology
• Adrenoleukodystrophy/genetics
• Induced Pluripotent Stem Cells/metabolism
• Astrocytes/metabolism
• Astrocytes/pathology
• ATP Binding Cassette Transporter, Subfamily D, Member 1/genetics
• Neurons/metabolism
• Neurons/pathology
• Coculture Techniques
• Cells, Cultured
• Fibroblasts/metabolism
• Fibroblasts/pathology
• Lipid Metabolism
• Male
• Fatty Acids/metabolism

• 2019-020C2 Association Européenne contre les Leucodystrophies
• 2023-102 Stichting Metakids
• 016.196.310 Nederlandse Organisatie voor Wetenschappelijk Onderzoek
• Amsterdam UMC (FlexOIO)
• Association Européenne contre les Leucodystrophies
• Stichting Metakids
• Nederlandse Organisatie voor Wetenschappelijk Onderzoek

• 543002004 ZonMw (Netherlands Organisation for Health Research and Development)
• 016.196.310 Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)

• 4D-Lipidomics
• adrenoleukodystrophy
• parallel accumulation serial fragmentation
• trapped ion mobility spectrometry
• very-long-chain fatty acids

• Adrenoleukodystrophy/metabolism
• Adrenoleukodystrophy/genetics
• Humans
• Lipidomics/methods
• Ion Mobility Spectrometry
• Lipids/analysis
• Lipid Metabolism

• corneocyte lipid envelope (CLE)
• integrity of skin barrier
• mass spectrometry (MS) analysis
• omega-hydroxy ceramides (ω-OH-Cer)
• skin care

• acyl CoA synthetase
• fatty acid transport protein 4
• fatty acids
• lipidomics
• phospholipids
• triglycerides

• Animals
• CD36 Antigens/metabolism
• Fatty Acid Transport Proteins/genetics
• Fatty Acid Transport Proteins/metabolism
• Fatty Acid-Binding Proteins/metabolism
• Fatty Acids/metabolism
• Humans
• Lipids
• Liver Diseases
• Membrane Transport Proteins
• Mice
• Obesity/genetics
• Triglycerides

• Adrenoleukodystrophy
• Dietary lipids
• Fibroblasts
• Monounsaturated fatty acids
• Peroxisomes
• Sphingomyelin
• Very long-chain fatty acids

• Adrenoleukodystrophy/drug therapy
• Child
• Fatty Acids/metabolism
• Fatty Acids/therapeutic use
• Fatty Acids, Monounsaturated/metabolism
• Fatty Acids, Monounsaturated/therapeutic use
• Fibroblasts
• Humans

• R21 TR003941 NCATS NIH HHS
• National Center for Advancing Translational Sciences
• United Leukodystrophy Foundation

• Astrocytes
• Endothelium
• Leukodystrophy
• Microglia
• Myelin
• Neurovascular unit
• Oligodendrocyte
• Pericyte
• White matter

• Adolescent
• Adult
• Aged
• Alexander Disease/genetics
• Alexander Disease/pathology
• Autoimmune Diseases of the Nervous System/genetics
• Autoimmune Diseases of the Nervous System/pathology
• Blood-Brain Barrier/pathology
• Child
• Child, Preschool
• Female
• Humans
• Leukodystrophy, Metachromatic/genetics
• Leukodystrophy, Metachromatic/pathology
• Male
• Nervous System Malformations/genetics
• Nervous System Malformations/pathology
• Neurovascular Coupling/physiology
• Pelizaeus-Merzbacher Disease/genetics
• Pelizaeus-Merzbacher Disease/pathology

• ZonMW

• fatty acids
• inborn error of metabolism
• model systems
• pathogenesis
• peroxisomes

• ATP Binding Cassette Transporter, Subfamily D, Member 1/genetics
• Adrenoleukodystrophy/epidemiology
• Adrenoleukodystrophy/genetics
• Adult
• Animals
• Biological Evolution
• Fatty Acids/metabolism
• Female
• Humans
• Male
• Models, Animal
• Models, Biological
• Mutation
• Sex Factors
• Spinal Cord Diseases/epidemiology

• Association Européenne contre les Leucodystrophies
• Nederlandse Organisatie voor Wetenschappelijk Onderzoek

• Fatty acid oxidation
• Metabolism
• Neuroscience

• BMP, Bis(monoacylglycero) phosphate
• Cer-NS, Ceramide nonhydroxyfatty acid-sphingosines
• Fragile X syndrome
• GL, Glycerolipid
• HexCer-NS, Hexosylceramide nonhydroxyfatty acid-sphingosines
• LPC, Lysophosphatidylcholines
• Lipidomics
• Metabolomics
• Microdeletion
• PC, Phosphatidylcholine
• PE, Phosphatidylethanolamine
• PG, Phosphatidylglycerol
• SM, Sphingomyelin
• SP, Sphingolipid
• ST, Sterol
• Xq27.3-Xq28

• Adrenal failure
• Gonadal insufficiency
• Leukodystrophy
• Myelopathy
• Peripheral neuropathy
• Peroxisomal disorders
• Schilder's disease
• VLCFA
• Very long-chain fatty acids
• X-linked adrenoleukodystrophy

• Adolescent
• Adrenoleukodystrophy/genetics
• Adrenoleukodystrophy/therapy
• Adult
• Fatty Acids
• Female
• Humans
• Male
• Mutation/genetics
• Spinal Cord Diseases

• U54 NS115052 NINDS NIH HHS

X-linked adrenoleukodystrophy (X-ALD), an inborn error of peroxisomal β-oxidation, is caused by defects in the ATP Binding Cassette Subfamily D Member 1 (ABCD1) gene. X-ALD patients may be asymptomatic or present with several clinical phenotypes varying from severe to mild, severe cerebral adrenoleuko-dystrophy to mild adrenomyeloneuropathy (AMN). Although most female heterozygotes present with AMN-like symptoms after 60 years of age, occasional cases of females with the cerebral form have been reported. Phenotypic variability has been described within the same kindreds and even among monozygotic twins. There is no association between the nature of ABCD1 mutation and the clinical phenotypes, and the molecular basis of phenotypic variability in X-ALD is yet to be resolved. Various genetic, epigenetic, and environmental influences are speculated to modify the disease onset and severity. In this review, we summarize the observations made in various studies investigating the potential modifying factors regulating the clinical manifestation of X-ALD, which could help understand the pathogenesis of the disease and develop suitable therapeutic strategies.

• X-adrenoleukodystrophy
• Cerebral adrenoleukodystrophy
• Adrenomyelo-neuropathy
• Phenotypic variation
• Modifiers

ACBD5 deficiency is a novel peroxisome disorder with a largely uncharacterized pathology. ACBD5 was recently identified in a tethering complex mediating membrane contacts between peroxisomes and the endoplasmic reticulum (ER). An ACBD5-deficient mouse was analyzed to correlate ACBD5 tethering functions with the disease phenotype. ACBD5-deficient mice exhibit elevated very long-chain fatty acid levels and a progressive cerebellar pathology. Liver did not exhibit pathologic changes but increased peroxisome abundance and drastically reduced peroxisome-ER contacts. Lipidomics of liver and cerebellum revealed tissue-specific alterations in distinct lipid classes and subspecies. In line with the neurological pathology, unusual ultra-long chain fatty acids (C > 32) were elevated in phosphocholines from cerebelli but not liver indicating an organ-specific imbalance in fatty acid degradation and elongation pathways. By contrast, ether lipid formation was perturbed in liver towards an accumulation of alkyldiacylglycerols. The alterations in several lipid classes suggest that ACBD5, in addition to its acyl-CoA binding function, might maintain peroxisome-ER contacts in order to contribute to the regulation of anabolic and catabolic cellular lipid pathways.

Darwisch, von Spangenberg et al. show that ACBD5‐deficient mice exhibit elevated levels of very long‐chain fatty acids and a progressive cerebellar pathology. A complex metabolic phenotype suggests that ACBD5 with its acyl‐CoA binding and peroxisome‐ER tethering functions might contribute to the regulation of anabolic and catabolic cellular lipid pathways.

• fatty acid elongation
• lipid homeostasis
• sphingolipid
• very long chain fatty acid.

• Acyl-CoA binding domain containing protein
• FFAT motif
• Lipid metabolism
• Membrane contact sites
• Pathogen host interaction
• Peroxisomes

• Animals
• Carrier Proteins/chemistry
• Carrier Proteins/genetics
• Carrier Proteins/metabolism
• Evolution, Molecular
• Fungal Proteins/chemistry
• Fungal Proteins/genetics
• Fungal Proteins/metabolism
• Fungi/chemistry
• Fungi/genetics
• Fungi/metabolism
• Lipid Metabolism
• Models, Molecular
• Neoplasms/metabolism
• Phylogeny
• Protein Conformation
• Protein Domains

• MR/N0137941/1 Medical Research Council
• BB/M011801/1 Biotechnology and Biological Sciences Research Council
• MR/T019409/1 Medical Research Council
• BB/N01541X/1 Biotechnology and Biological Sciences Research Council
• BB/P003818/1 Biotechnology and Biological Sciences Research Council
• BB/T002255/1 Biotechnology and Biological Sciences Research Council
• CIC 08135 Medical Research Council

• Adrenomyeloneuropathy
• Childhood cerebral adrenoleukodystrophy
• Lipidomics
• Transcriptomics
• X-linked adrenoleukodystrophy

• Adrenoleukodystrophy
• Endoplasmic reticulum stress
• Fatty acids
• Lipotoxicity
• Neurodegeneration

The activation of the highly conserved unfolded protein response (UPR) is prominent in the pathogenesis of the most prevalent neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), which are classically characterized by an accumulation of aggregated or misfolded proteins. This activation is orchestrated by three endoplasmic reticulum (ER) stress sensors: PERK, ATF6 and IRE1. These sensors transduce signals that induce the expression of the UPR gene programme. Here, we first identified an early activator of the UPR and investigated the role of a chronically activated UPR in the pathogenesis of X-linked adrenoleukodystrophy (X-ALD), a neurometabolic disorder that is caused by ABCD1 malfunction; ABCD1 transports very long-chain fatty acids (VLCFA) into peroxisomes. The disease manifests as inflammatory demyelination in the brain or and/or degeneration of corticospinal tracts, thereby resulting in spastic paraplegia, with the accumulation of intracellular VLCFA instead of protein aggregates. Using X-ALD mouse model (Abcd1⁻ and Abcd1⁻/Abcd2^−/− mice) and X-ALD patient’s fibroblasts and brain samples, we discovered an early engagement of the UPR. The response was characterized by the activation of the PERK and ATF6 pathways, but not the IRE1 pathway, showing a difference from the models of AD, PD or ALS. Inhibition of PERK leads to the disruption of homeostasis and increased apoptosis during ER stress induced in X-ALD fibroblasts. Redox imbalance appears to be the mechanism that initiates ER stress in X-ALD. Most importantly, we demonstrated that the bile acid tauroursodeoxycholate (TUDCA) abolishes UPR activation, which results in improvement of axonal degeneration and its associated locomotor impairment in Abcd1⁻/Abcd2^−/− mice. Altogether, our preclinical data provide evidence for establishing the UPR as a key drug target in the pathogenesis cascade. Our study also highlights the potential role of TUDCA as a treatment for X-ALD and other axonopathies in which similar molecular mediators are implicated.

• Adrenoleukodystrophy
• ER stress
• Neurodegeneration
• Oxidative stress
• Peroxisome
• TUDCA
• UPR

• Beta-oxidation
• Elongation
• Fatty acids
• Peroxisome
• Stable-isotope
• Very-long-chain fatty acids

• Cell Culture Techniques
• Cells, Cultured
• Fatty Acids/metabolism
• Fibroblasts/metabolism
• Humans
• Isotopes
• Lipid Metabolism
• Oxidation-Reduction
• Peroxisomes/metabolism

• ATP Binding Cassette Transporter, Subfamily D, Member 1
• ATP-Binding Cassette Transporters/genetics
• ATP-Binding Cassette Transporters/metabolism
• Adrenal Insufficiency/metabolism
• Adrenoleukodystrophy/diagnosis
• Adrenoleukodystrophy/drug therapy
• Adrenoleukodystrophy/genetics
• Adrenoleukodystrophy/metabolism
• Brain/diagnostic imaging
• Disease Progression
• Fatty Acids/metabolism
• Female
• Glucocorticoids/therapeutic use
• Hormone Replacement Therapy
• Humans
• Leukoencephalopathies/diagnostic imaging
• Leukoencephalopathies/metabolism
• Male
• Peripheral Nervous System Diseases/metabolism
• Spinal Cord Diseases/metabolism

• Adrenoleukodystrophy
• Cytochrome P450
• Dicarboxylic acids
• Modifier gene
• Omega-oxidation
• Peroxisomes

• Carrier testing
• Diagnosis
• Metabolic disease
• Peroxisome

• ATP Binding Cassette Transporter, Subfamily D, Member 1/genetics
• ATP Binding Cassette Transporter, Subfamily D, Member 1/metabolism
• Adrenoleukodystrophy/blood
• Adrenoleukodystrophy/diagnosis
• Adrenoleukodystrophy/genetics
• Adult
• Alleles
• Cell Line
• DNA Mutational Analysis
• Fatty Acids/blood
• Female
• Genetic Carrier Screening/methods
• Genetic Variation
• Humans
• Male
• Middle Aged
• Mutation
• Peroxisomes/metabolism
• Spinal Cord Diseases/diagnosis
• Spinal Cord Diseases/genetics

• erucic acid
• inborn errors of metabolism
• nonmem
• population pharmacodynamics

• Acyl-CoA synthetase
• Bubblegum
• Double bubble
• Drosophila
• Neurodegeneration
• SLC27a6
• VLCFA

• Differential expression
• Inflammation
• Phenotype
• X-ALD
• miRNA

• ABCD1
• Microsomal fatty acid elongation
• Very long chain fatty acid
• X-linked adrenoleukodystrophy

• ATP Binding Cassette Transporter, Subfamily D, Member 1
• ATP-Binding Cassette Transporters/deficiency
• Adrenoleukodystrophy
• Animals
• Brain Chemistry/genetics
• Enzyme Inhibitors/pharmacology
• Ethylmaleimide/pharmacology
• Fatty Acids/metabolism
• L-Lactate Dehydrogenase/metabolism
• Lipid Metabolism/drug effects
• Lipid Metabolism/genetics
• Male
• Malonyl Coenzyme A/antagonists & inhibitors
• Malonyl Coenzyme A/metabolism
• Mice
• Mice, Inbred C57BL
• Microsomes/metabolism
• Myelin Sheath/genetics

Biochemical changes associated with multiple sclerosis (MS), and its various clinical forms have not been characterized well. Therefore, we investigated the biochemistry of MS in relation to its natural history using targeted lipidomics platforms.

Cross-sectional serum samples from 24 secondary progressive (SPMS), 100 relapsing remitting (RRMS), 19 primary progressive MS (PPMS), and 55 age-matched control subjects were analyzed by flow injection tandem mass spectrometry for very long chain fatty acid (VLCFA) containing phosphatidyl ethanolamines (PtdEtn), plasmalogen ethanolamines (PlsEtn) and for novel anti-inflammatory gastrointestinal tract acids (GTAs). Changes in analyte levels relative to healthy controls were correlated with the disease stage and disease duration.

RRMS subjects having <13 years disease duration had elevated levels (p < 0.05) of anti-inflammatory metabolites (GTAs) and normal levels (p > 0.05) of mitochondrial stress biomarkers (VLCFA-PtdEtn), compared to controls. SPMS subjects had statistically similar levels of anti-inflammatory metabolites (GTAs), elevated mitochondrial stress metabolites (VLCFA-PtdEtn) and elevated peroxisomal metabolites (PlsEtn) compared to controls (p < 0.05). RRMS subjects with > = 13 years disease duration exhibited metabolic profiles intermediate between short-duration RRMS and SPMS, based on statistical significance. Therefore, RRMS cohort appear to comprise of two metabolically distinct subpopulations. The key clinical discriminator of these two groups was disease duration. PPMS patients exhibited metabolic profiles distinct from RRMS and SPMS.

These data indicate that inflammation and mitochondrial stress are intricately involved in the etiology of MS and that progression in MS can potentially be monitored using serum metabolic biomarkers.

• X-linked Adrenoleukodystrophy
• drug therapy
• gene expression
• mitochondria
• peroxisomes
• suberoylanilide hydroxamic acid

Currently the molecular basis for the clinical heterogeneity of X-linked adrenoleukodystrophy (X-ALD) is poorly understood. The genetic bases for all different phenotypic variants of X-ALD are mutations in the gene encoding the peroxisomal ATP-binding cassette (ABC) transporter, ABCD1 (formerly adrenoleukodystrophy protein, ALDP). ABCD1 transports CoA-activated very long-chain fatty acids from the cytosol into the peroxisome for degradation. The phenotypic variability is remarkable ranging from cerebral inflammatory demyelination of childhood onset, leading to death within a few years, to adults remaining pre-symptomatic through more than five decades. There is no general genotype–phenotype correlation in X-ALD. The default manifestation of mutations in ABCD1 is adrenomyeloneuropathy, a slowly progressive dying-back axonopathy affecting both ascending and descending spinal cord tracts as well as in some cases, a peripheral neuropathy. In about 60% of male X-ALD patients, either in childhood (35–40%) or in adulthood (20%), an initial, clinically silent, myelin destabilization results in conversion to a devastating, rapidly progressive form of cerebral inflammatory demyelination. Here, ABCD1 remains a susceptibility gene, necessary but not sufficient for inflammatory demyelination to occur. Although the accumulation of very long-chain fatty acids appears to be essential for the pathomechanism of all phenotypes, the molecular mechanisms underlying these phenotypes are fundamentally different. Cell autonomous processes such as oxidative stress and energy shortage in axons as well as non-cell autonomous processes involving axon–glial interactions seem pertinent to the dying-back axonopathy. Various dynamic mechanisms may underlie the initiation of inflammation, the altered immune reactivity, the propagation of inflammation, as well as the mechanisms leading to the arrest of inflammation after hematopoietic stem cell transplantation. An improved understanding of the molecular mechanisms involved in these events is required for the development of urgently needed therapeutics.

•

Adrenomyeloneuropathy (AMN) is proposed to be the core syndrome of X-ALD.

• ABC transporter
• Axonopathy
• Demyelination
• Inflammation
• Leukodystrophy
• Peroxisome

In X-ALD, mutation/deletion of ALD gene (ABCD1) and the resultant very long chain fatty acid (VLCFA) derangement has dramatically opposing effects in astrocytes and oligodendrocytes. While loss of Abcd1 in astrocytes produces a robust inflammatory response, the oligodendrocytes undergo cell death leading to demyelination in X-linked adrenoleukodystrophy (X-ALD). The mechanisms of these distinct pathways in the two cell types are not well understood. Here, we investigated the effects of Abcd1-knockdown and the subsequent alteration in VLCFA metabolism in human U87 astrocytes and rat B12 oligodendrocytes. Loss of Abcd1 inhibited peroxisomal β-oxidation activity and increased expression of VLCFA synthesizing enzymes, elongase of very long chain fatty acids (ELOVLs) (1 and 3) in both cell types. However, higher induction of ELOVL's in Abcd1-deficient B12 oligodendrocytes than astrocytes suggests that ELOVL pathway may play a prominent role in oligodendrocytes in X-ALD. While astrocytes are able to maintain the cellular homeostasis of anti-apoptotic proteins, Abcd1-deletion in B12 oligodendrocytes downregulated the anti-apototic (Bcl-2 and Bcl-xL) and cell survival (phospho-Erk1/2) proteins, and upregulated the pro-apoptotic proteins (Bad, Bim, Bax and Bid) leading to cell loss. These observations provide insights into different cellular signaling mechanisms in response to Abcd1-deletion in two different cell types of CNS. The apoptotic responses were accompanied by activation of caspase-3 and caspase-9 suggesting the involvement of mitochondrial-caspase-9-dependent mechanism in Abcd1-deficient oligodendrocytes. Treatment with histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) corrected the VLCFA derangement both in vitro and in vivo, and inhibited the oligodendrocytes loss. These observations provide a proof-of principle that HDAC inhibitor SAHA may have a therapeutic potential for X-ALD.

• Animals
• Apoptosis/drug effects
• Fatty Acids/metabolism
• Histone Deacetylase Inhibitors/pharmacology
• Humans
• Oxidation-Reduction
• Peroxisomes/metabolism
• Rats

• R01 NS022576 NINDS NIH HHS
• R37 NS022576 NINDS NIH HHS
• NS-22576 NINDS NIH HHS
• C06 RR018823 NCRR NIH HHS
• NS-37766 NINDS NIH HHS
• R01 NS037766 NINDS NIH HHS
• I01 BX001072 BLRD VA
• C06 RR015455 NCRR NIH HHS

• Child
• Female
• Humans
• Male
• Peroxisomal Disorders/diagnosis
• Peroxisomal Disorders/genetics
• Peroxisomal Disorders/metabolism
• Pregnancy
• Prenatal Diagnosis

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. The disease is caused by mutations in the ABCD1 gene that encodes the peroxisomal membrane protein ALDP which is involved in the transmembrane transport of very long-chain fatty acids (VLCFA; ≥C22). A defect in ALDP results in elevated levels of VLCFA in plasma and tissues. The clinical spectrum in males with X-ALD ranges from isolated adrenocortical insufficiency and slowly progressive myelopathy to devastating cerebral demyelination. The majority of heterozygous females will develop symptoms by the age of 60 years. In individual patients the disease course remains unpredictable. This review focuses on the diagnosis and management of patients with X-ALD and provides a guideline for clinicians that encounter patients with this highly complex disorder.

This is a case report of adrenomyeloneuropathy (AMN), the adult variant of adrenoleukodystryphy (ALD). The diagnoses in the patient, aged 34, was confirmed via increased serum very long chain fatty acid concentration (VLCFA). Treatment started with the cholesterol lowering drug, atorvastatin, followed by add-on therapy with Lorenzo's oil (LO) and finally supplementation with docosahexaenoic acid (DHA). The magnetic resonance imaging (MRI) scan of the AMN patient before DHA treatment, already showed abnormal white matter in the brain. Although the MRI showed no neurological improvement after 6 months of DHA treatment, no selective progression of demyelination was detected in the AMN patient. Contrary to what was expected, LO failed to sustain or normalize the VLCFA levels or improve clinical symptoms. It was however, shown that DHA supplementation in addition to LO, increased DHA levels in both plasma and red blood cells (RBC). Additionally, the study showed evidence that the elongase activity in the elongation of eicosapentaenoic acid (EPA) to docosapentaenoic acid (DPA) might have been significantly compromised, due to the increased DHA levels.

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene encoding the peroxisomal ABC transporter adrenoleukodystrophy protein (ALDP). X-ALD is characterized by the accumulation of very long-chain fatty acids (VLCFA; ≥C24) in plasma and tissues. In this manuscript we provide insight into the pathway underlying the elevated levels of C26:0 in X-ALD. ALDP transports VLCFacyl-CoA across the peroxisomal membrane. A deficiency in ALDP impairs peroxisomal β-oxidation of VLCFA but also raises cytosolic levels of VLCFacyl-CoA which are substrate for further elongation. We identify ELOVL1 (elongation of very-long-chain-fatty acids) as the single elongase catalysing the synthesis of both saturated VLCFA (C26:0) and mono-unsaturated VLCFA (C26:1). ELOVL1 expression is not increased in X-ALD fibroblasts suggesting that increased levels of C26:0 result from increased substrate availability due to the primary deficiency in ALDP. Importantly, ELOVL1 knockdown reduces elongation of C22:0 to C26:0 and lowers C26:0 levels in X-ALD fibroblasts. Given the likely pathogenic effects of high C26:0 levels, our findings highlight the potential of modulating ELOVL1 activity in the treatment of X-ALD.

• Adrenoleukodystrophy/metabolism
• Biological Transport
• Cell Line
• Cell Membrane/chemistry
• Cell Membrane/metabolism
• Diffusion
• Eicosanoic Acids/chemistry
• Eicosanoic Acids/metabolism
• Fatty Acids/chemistry
• Fatty Acids/metabolism
• Fluorescent Dyes/chemistry
• Humans
• Lipid Bilayers/chemistry
• Lipid Bilayers/metabolism
• Phosphatidylcholines/chemistry
• Phosphatidylcholines/metabolism
• Spectrometry, Fluorescence
• beta-Cyclodextrins/chemistry

• P01 HL026335 NHLBI NIH HHS
• 2P01 HL26335-21 NHLBI NIH HHS

• Adolescent
• Astrocytes/drug effects
• Autistic Disorder/blood
• Autistic Disorder/metabolism
• Autistic Disorder/pathology
• Biomarkers/blood
• Biomarkers/metabolism
• Child
• Child, Preschool
• Cysteine/metabolism
• Fatty Acids/blood
• Fatty Acids/metabolism
• Female
• Glutamic Acid/pharmacology
• Glutathione/metabolism
• Hepatocytes/drug effects
• Humans
• Male
• Methionine/metabolism
• Mitochondria/metabolism
• Mitochondria/pathology
• Neurons/drug effects
• Phospholipids/blood
• Phospholipids/metabolism
• Siblings

• Adrenoleukodystrophy/metabolism
• Adrenoleukodystrophy/therapy
• Amyotrophic Lateral Sclerosis/therapy
• Animals
• Antioxidants/therapeutic use
• Drug Combinations
• Erucic Acids/therapeutic use
• Free Radical Scavengers/therapeutic use
• Humans
• Oxidative Stress
• Reactive Oxygen Species
• Triolein/therapeutic use