Back to Search
Start Over
Nuclear lipidome is altered in amyotrophic lateral sclerosis: A pilot study
- Source :
- Journal of neurochemistryREFERENCES. 158(2)
- Publication Year :
- 2021
-
Abstract
- Nucleocytosolic transport, a membrane process, is impaired in motor neurons in amyotrophic lateral sclerosis (ALS). This study analyzes the nuclear lipidome in motor neurons in ALS and examines molecular pathways linked to the major lipid alterations. Nuclei were obtained from the frozen anterior horn of the lumbar spinal cord of ALS patients and age-matched controls. Lipidomic profiles of this subcellular fraction were obtained using liquid chromatography and mass spectrometry. We validated the mechanisms behind presumable lipidomic changes by exploring ALS surrogate models including human motor neurons (derived from ALS lines and controls) subjected to oxidative stress, the hSOD-G93A transgenic mice, and samples from an independent cohort of ALS patients. Among the differential lipid species, we noted 41 potential identities, mostly belonging to phospholipids (particularly ether phospholipids, as plasmalogens), as well as diacylglycerols and triacylglycerides. Decreased expression of alkyldihydroxyacetonephosphate synthase (AGPS)-a critical peroxisomal enzyme in plasmalogen synthesis-is found in motor neuron disease models; this occurs in parallel with an increase in the expression of sterol carrier protein 2 (SCP2) mRNA in ALS and Scp2 levels in G93A transgenic mice. Further, we identified diminished expression of diacylglycerol-related enzymes, such as phospholipase C βI (PLCβI) and protein kinase CβII (PKCβII), linked to diacylglycerol metabolism. Finally, lipid droplets were recognized in the nuclei, supporting the identification of triacylglycerides as differential lipids. Our results point to the potentially pathogenic role of altered composition of nuclear membrane lipids and lipids in the nucleoplasm in the anterior horn of the spinal cord in ALS. Overall, these data support the usefulness of subcellular lipidomics applied to neurodegenerative diseases.
- Subjects :
- 0301 basic medicine
Male
Plasmalogen
Mice, Transgenic
Pilot Projects
Biochemistry
Diglycerides
03 medical and health sciences
Cellular and Molecular Neuroscience
Mice
0302 clinical medicine
Cytosol
Superoxide Dismutase-1
Lipid droplet
Lipidomics
medicine
Animals
Humans
Amyotrophic lateral sclerosis
Aged
Cell Nucleus
Motor Neurons
Phospholipase C
Chemistry
Amyotrophic Lateral Sclerosis
Cell Membrane
Lipidome
Motor neuron
Middle Aged
medicine.disease
Cell biology
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Sterol carrier protein
Spinal Cord
lipids (amino acids, peptides, and proteins)
Female
Carrier Proteins
030217 neurology & neurosurgery
Subcellular Fractions
Subjects
Details
- ISSN :
- 14714159
- Volume :
- 158
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of neurochemistryREFERENCES
- Accession number :
- edsair.doi.dedup.....fd01c8629498009c14f4fff0ab7b4c2f