Increased lipid droplet accumulation associated with a peripheral sensory neuropathy.
Hereditary sensory neuropathy type 1 (HSN-1) is an autosomal dominant neurodegenerative disease caused by missense mutations in the SPTLC1 gene. The SPTLC1 protein is part of the SPT enzyme which is a ubiquitously expressed, critical and thus highly regulated endoplasmic reticulum bound membrane enzyme that maintains sphingolipid concentrations and thus contributes to lipid metabolism, signalling, and membrane structural functions. Lipid droplets are dynamic organelles containing sphingolipids and membrane bound proteins surrounding a core of neutral lipids, and thus mediate the intracellular transport of these specific molecules. Current literature suggests that there are increased numbers of lipid droplets and alterations of lipid metabolism in a variety of other autosomal dominant neurodegenerative diseases, including Alzheimer's and Parkinson's disease. This study establishes for the first time, a significant increase in the presence of lipid droplets in HSN-1 patient-derived lymphoblasts, indicating a potential connection between lipid droplets and the pathomechanism of HSN-1. However, the expression of adipophilin (ADFP), which has been implicated in the regulation of lipid metabolism, was not altered in lipid droplets from the HSN-1 patient-derived lymphoblasts. This appears to be the first report of increased lipid body accumulation in a peripheral neuropathy, suggesting a fundamental molecular linkage between a number of neurodegenerative diseases.
Neuro-Cell Biology Laboratory, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; Molecular Medicine Research Group, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia.
Lee L
LL
Marshall
Neuro-Cell Biology Laboratory, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; Molecular Medicine Research Group, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia.
Scott E
SE
Stimpson
Neuro-Cell Biology Laboratory, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; Molecular Medicine Research Group, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia.
Ryan
R
Hyland
Molecular Physiology, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; Molecular Medicine Research Group, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; University of Western Sydney, Office 30.2.15, Campbelltown campus, Locked Bag 1797, Penrith South DC, NSW 1797 Australia.
Jens R
JR
Coorssen
Molecular Medicine Research Group, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797 Australia ; University of Western Sydney, Office 21.1.05, Campbelltown campus, Locked Bag 1797, Penrith South DC, NSW 1797 Australia.
Simon J
SJ
Myers
ADFP; Hereditary sensory neuropathy type 1; Lipid droplets; Nile red; Serine palmitoyltransferase; Serine palmitoyltransferase long chain subunit 1