BioE COLLOQUIA SERIES: "1-Deoxy-Sphingolipids – When Sphingolipids Become Headless"
Event details
| Date | 23.09.2019 |
| Hour | 12:15 |
| Speaker | Prof. Thorsten Hornemann, University of Zürich (CH) |
| Location | |
| Category | Conferences - Seminars |
WEEKLY BIOENGINEERING COLLOQUIA SERIES
(sandwiches served)
Abstract:
1-DeoxySphingolipids (1-deoxySL) are atypical sphingolipids, which are formed due to a shift in the substrate preference of the serine palmitoyltransferase (SPT). 1-DeoxySL lack the C1 hydroxyl group of normal sphingolipids, which precludes their conversion to complex sphingolipids but also their further downstream metabolism. The rare axonal neuropathy HSAN1 is caused by pathologically increased 1-deoxySL levels due to mutations in SPT. 1-DeoxySLs are toxic to neurons in culture, induce neurite retraction and disrupt neuronal structures, likely by interfering with regulatory components of the cytoskeleton. At increased L-serine concentrations, 1-deoxySL formation is significantly suppressed. HSAN1 mice, which received an L-serine enriched diet, showed normal 1-deoxySL levels and did not develop neuropathic symptoms. 1-DeoxySL are also elevated in type 2 diabetes and associated with beta cell dysfunction, wound healing defects and the diabetic sensory neuropathy (DSN). L-serine supplementation significantly improved neuropathy in diabetic rats. Although 1-deoxySL cannot be degraded by the canonical sphingolipid catabolism, they appear to be metabolized by a set of desaturases and CYP4F enzymes, which likely reflects a physiological detoxification mechanism. CYP4F expression is reduced in obesity whereas PPARαantagonists, such as fibrates, induce the expression of these enzymes and lower 1-deoxySL levels. Trageting CYP4F enzymes could therefore be a novel therapeutic approach in DSN.
Research overview:
The main field of our research is the influence of sphigolipid metabolism on cellular signalling and apoptosis. Ceramides and metabolites thereof are ubiquitous constituents of membrane lipids in mammalian cells and involved in various cellular events like apoptosis, signal transduction and membrane trafficking. A dysfunctuion of the ceramide pathway is the cause for various deseases like HSN1 or Fabry. In our research we investigate the role of de novo sphingolipid synthesis on peripheral neuronal development and axonal regeneration as well as its possible influence in other neurodegenerative diseases like diabetic sensory neuropathy (DSN) or Alzheimer desease. Currently the main focus of our work is the function and regulation of the serine-palmitoyltransferase, a keyenzyme in the de-novo synthesis pathway of sphingolipids.
(sandwiches served)
Abstract:
1-DeoxySphingolipids (1-deoxySL) are atypical sphingolipids, which are formed due to a shift in the substrate preference of the serine palmitoyltransferase (SPT). 1-DeoxySL lack the C1 hydroxyl group of normal sphingolipids, which precludes their conversion to complex sphingolipids but also their further downstream metabolism. The rare axonal neuropathy HSAN1 is caused by pathologically increased 1-deoxySL levels due to mutations in SPT. 1-DeoxySLs are toxic to neurons in culture, induce neurite retraction and disrupt neuronal structures, likely by interfering with regulatory components of the cytoskeleton. At increased L-serine concentrations, 1-deoxySL formation is significantly suppressed. HSAN1 mice, which received an L-serine enriched diet, showed normal 1-deoxySL levels and did not develop neuropathic symptoms. 1-DeoxySL are also elevated in type 2 diabetes and associated with beta cell dysfunction, wound healing defects and the diabetic sensory neuropathy (DSN). L-serine supplementation significantly improved neuropathy in diabetic rats. Although 1-deoxySL cannot be degraded by the canonical sphingolipid catabolism, they appear to be metabolized by a set of desaturases and CYP4F enzymes, which likely reflects a physiological detoxification mechanism. CYP4F expression is reduced in obesity whereas PPARαantagonists, such as fibrates, induce the expression of these enzymes and lower 1-deoxySL levels. Trageting CYP4F enzymes could therefore be a novel therapeutic approach in DSN.
Research overview:
The main field of our research is the influence of sphigolipid metabolism on cellular signalling and apoptosis. Ceramides and metabolites thereof are ubiquitous constituents of membrane lipids in mammalian cells and involved in various cellular events like apoptosis, signal transduction and membrane trafficking. A dysfunctuion of the ceramide pathway is the cause for various deseases like HSN1 or Fabry. In our research we investigate the role of de novo sphingolipid synthesis on peripheral neuronal development and axonal regeneration as well as its possible influence in other neurodegenerative diseases like diabetic sensory neuropathy (DSN) or Alzheimer desease. Currently the main focus of our work is the function and regulation of the serine-palmitoyltransferase, a keyenzyme in the de-novo synthesis pathway of sphingolipids.
Practical information
- Informed public
- Free
Organizer
Contact
- Institute of Bioengineering (IBI), Christina Mattsson