ArticleThe Journal of biological chemistry2010
Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers.
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Who cites it
199 citing papers in PubMed, 373 citations in OpenAlex.
- Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1.Neurology · 2019Trial
- Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Trial
- 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
- Mechanisms of deoxysphinganine cytotoxicity in lymphoma cells.Journal of lipid research · 2026Article
- Deletion of exon 2 in ALS-linkedLife science alliance · 2026Article
- Convergent human genetic evidence implicates serine biosynthesis in diabetic peripheral neuropathy.medRxiv : the preprint server for health sciences · 2026Article
- Antisense oligonucleotides reverse SPTLC1-related hereditary sensory neuropathy in a mouse model.Brain : a journal of neurology · 2026Article
- Spectrum of dominant Charcot-Marie-Tooth disease due toJournal of neurology, neurosurgery, and psychiatry · 2026Article
- Lipid alterations in hereditary peripheral neuropathies: common mechanisms in disease heterogeneity?Molecular neurodegeneration · 2026Review
- Charcot-Marie-Tooth disease and related neuropathies.Nature reviews. Disease primers · 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
- Lipid ciliology: specialized ciliary membrane lipids in physiology and disease.Frontiers in cell and developmental biology · 2026Review
- Blood 1-Deoxysphingolipid Levels Are Associated With Epidermal Denervation in Small Fiber Neuropathy.Journal of the peripheral nervous system : JPNS · 2025Article
- Review
- Very long-chain fatty acids drive 1-deoxySphingolipid toxicity.Nature communications · 2025Article
- The Involvement of Ceramide, Sphingosine-1-Phosphate and Ganglioside GM1 in Regulating Some Nervous System Functions.International journal of molecular sciences · 2025Review
- Individual lipid alterations at the origin of neuronal Ceramide Synthase defects.PLoS genetics · 2025Article
- Article
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
139 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 4 countries.
Funding
Abstract
HSAN1 is an inherited neuropathy found to be associated with several missense mutations in the SPTLC1 subunit of serine palmitoyltransferase (SPT). SPT catalyzes the condensation of serine and palmitoyl-CoA, the initial step in the de novo synthesis of sphingolipids. Here we show that the HSAN1 mutations induce a shift in the substrate specificity of SPT, which leads to the formation of the two atypical deoxy-sphingoid bases (DSBs) 1-deoxy-sphinganine and 1-deoxymethyl-sphinganine. Both metabolites lack the C(1) hydroxyl group of sphinganine and can therefore neither be converted to complex sphingolipids nor degraded. Consequently, they accumulate in the cell, as demonstrated in HEK293 cells overexpressing mutant SPTLC1 and lymphoblasts of HSAN1 patients. Elevated DSB levels were also found in the plasma of HSAN1 patients and confirmed in three groups of HSAN1 patients with different SPTLC1 mutations. The DSBs show pronounced neurotoxic effects on neurite formation in cultured sensory neurons. The neurotoxicity co-occurs with a disturbed neurofilament structure in neurites when cultured in the presence of DSBs. Based on these observations, we conclude that HSAN1 is caused by a gain of function mutation, which results in the formation of two atypical and neurotoxic sphingolipid metabolites.
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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.