ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Overexpression of the wild-type SPT1 subunit lowers desoxysphingolipid levels and rescues the phenotype of HSAN1.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 98 citations in OpenAlex.
- Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1.Neurology · 2019Trial
- Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1.The Journal of clinical investigation · 2011Trial
- Antisense oligonucleotides reverse SPTLC1-related hereditary sensory neuropathy in a mouse model.Brain : a journal of neurology · 2026Article
- Lipid alterations in hereditary peripheral neuropathies: common mechanisms in disease heterogeneity?Molecular neurodegeneration · 2026Review
- 1-deoxysphingolipids dysregulate membrane properties and cargo trafficking in the early secretory pathway.Cell chemical biology · 2026Article
- Clinical histopathology and pathogenesis of macular telangiectasia type 2.Progress in retinal and eye research · 2026Review
- Article
- Altered sphingolipid biosynthetic flux and lipoprotein trafficking contribute to trans-fat-induced atherosclerosis.Cell metabolism · 2025Article
- Age-dependent small fiber neuropathy: Mechanistic insights from animal models.Experimental neurology · 2024Review
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- Recurrent de novoJournal of neurology, neurosurgery, and psychiatry · 2024Article
- Serine Palmitoyltransferase (SPT)-related Neurodegenerative and Neurodevelopmental Disorders.Journal of neuromuscular diseases · 2024Review
- Review of Eukaryote Cellular Membrane Lipid Composition, with Special Attention to the Fatty Acids.International journal of molecular sciences · 2023Review
- Sources and Sinks of Serine in Nutrition, Health, and Disease.Annual review of nutrition · 2023Review
- SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia.Brain : a journal of neurology · 2023Article
- Sphingolipids in mitochondria-from function to disease.Frontiers in cell and developmental biology · 2023Review
- Precision mouse models of Yars/dominant intermediate Charcot-Marie-Tooth disease type C and Sptlc1/hereditary sensory and autonomic neuropathy type 1.Journal of anatomy · 2022Article
- [Genetic distribution in Chinese patients with hereditary peripheral neuropathy].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2022Article
- 1-Deoxysphingolipid synthesis compromises anchorage-independent growth and plasma membrane endocytosis in cancer cells.Journal of lipid research · 2022Article
- SPTLC1 variants associated with ALS produce distinct sphingolipid signatures through impaired interaction with ORMDL proteins.The Journal of clinical investigation · 2022Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutations in the SPTLC1 subunit of serine palmitoyltransferase (SPT) cause an adult-onset, hereditary sensory, and autonomic neuropathy type I (HSAN1). We previously reported that mice bearing a transgene-expressing mutant SPTLC1 (tgSPTLC1(C133W)) show a reduction in SPT activity and hyperpathia at 10 months of age. Now analyzed at a later age, we find these mice develop sensory loss with a distal small fiber neuropathy and peripheral myelinopathy. This phenotype is largely reversed when these mice are crossed with transgenic mice overexpressing wild-type SPTLC1 showing that the mutant SPTLC1 protein is not inherently toxic. Simple loss of SPT activity also cannot account for the HSAN1 phenotype, since heterozygous SPTLC1 knock-out mice have reduced SPT activity but are otherwise normal. Rather, the presence of two newly identified, potentially deleterious deoxysphingoid bases in the tgSPTLC1(C133W), but not in the wild-type, double-transgenic tgSPTLC1(WT + C133W) or SPTLC1(+/-) mice, suggests that the HSAN1 mutations alter amino acid selectivity of the SPT enzyme such that palmitate is condensed with alanine and glycine, in addition to serine. This observation is consistent with the hypothesis that HSAN1 is the result of a gain-of-function mutation in SPTLC1 that leads to accumulation of a toxic metabolite.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.