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An iPSC model of hereditary sensory neuropathy-1 reveals L-serine-responsive deficits in neuronal ganglioside composition and axoglial interactions

Abstract:

Hereditary sensory neuropathy type 1 (HSN1) is caused by mutations in the SPTLC1 or SPTLC2 sub-units of the enzyme serine palmitoyltransferase, resulting in the production of toxic 1-deoxysphingolipid bases (DSBs). We used induced pluripotent stem cells (iPSCs) from patients with HSN1 to determine whether endogenous DSBs are neurotoxic, patho-mechanisms of toxicity and response to therapy. HSN1 iPSC-derived sensory neurons (iPSCdSNs) endogenously produce neurotoxic DSBs. Complex gangliosides,...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.xcrm.2021.100345

Authors


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Institution:
University of Oxford
Division:
MSD
Sub department:
Clinical Neurosciences
Role:
Author
ORCID:
0000-0002-0836-6328
More by this author
Institution:
University of Oxford
Division:
MSD
Role:
Author
ORCID:
0000-0001-9237-5878
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Role:
Author
European Pain Federation EFIC More from this funder
Publisher:
Cell Press Publisher's website
Journal:
Cell Reports Medicine Journal website
Volume:
2
Issue:
7
Article number:
100345
Publication date:
2021-07-20
Acceptance date:
2021-06-16
DOI:
EISSN:
2666-3791
Language:
English
Keywords:
Pubs id:
1182632
Local pid:
pubs:1182632
Deposit date:
2021-06-18

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