Home / Seminar & Event /Past Seminars / (339) “Ferroptosis: (patho)physiological relevance and pharmacological tractability”
Home / Seminar & Event /Past Seminars / (339) “Ferroptosis: (patho)physiological relevance and pharmacological tractability”
(339) “Ferroptosis: (patho)physiological relevance and pharmacological tractability”
Seminar: (339) “Ferroptosis: (patho)physiological relevance and pharmacological tractability”
Speaker: Prof. Marcus Conrad, Helmholtz Zentrum München, Institute of Developmental Genetics, Munich, Germany
Time: 2018-12-03 10:00 to 2018-12-03 11:30
Venue: Meeting room (406), Building 24
Organizer:

SPST


Abstract:  Ferroptosis is a non-apoptotic form of cell death characterized by an overshooting, iron-dependent lipid peroxidation. Ferroptosis is highly relevant not only for a number of degenerative diseases including ischemia/reperfusion injury and neurodegenerative disease, but also represents an attractive target for ferroptosis inducing strategies to combat chemotherapy-resistant tumor entities. Selenocysteine containing glutathione peroxidase (GPX4) is the key regulator of this form of cell death due to its unique activity to scavenge peroxides in lipid bilayers. The role of selenium in form of 21st amino acid selenocysteine has been recently shown to confer full stability towards peroxide-induced irreversible overoxidation and inactivation of GPX4 thereby preventing from ferroptosis in cells and mice. A specific type of inhibitory interneurons in the cortex of newborn mice emerged to require selenium-containing GPX4 thus representing the limiting factor for mammalian life. Recently, genome-wide reverse genetic screens identified acyl-CoA synthetase long-chain family member 4 (ACSL4) as an additional downstream member of the ferroptosis cascade, whose targeted knockout or pharmacological inhibition by thiazolidinediones conferred an unprecedented protection against ferroptosis in cells. In vivo studies are currently being performed to interrogate whether the combined deletion of GPX4 and ACSL4 mitigates tissue damage inflicted by the loss of GPX4 in ferroptosis-sensitive tissues. Moreover, gain-of function studies aim at unravelling yet-unrecognized players in the ferroptosis process. Hence, all these studies are geared towards providing a comprehensive picture whether or not certain ferroptosis players present viable targets for pharmacological intervention to prevent or induce ferroptosis in (neuro)degenerative disease and cancer, respectively.

(339) “Ferroptosis: (patho)physiological relevance and pharmacological tractability”
Seminar: (339) “Ferroptosis: (patho)physiological relevance and pharmacological tractability”
Speaker: Prof. Marcus Conrad, Helmholtz Zentrum München, Institute of Developmental Genetics, Munich, Germany
Time: 2018-12-03 10:00 to 2018-12-03 11:30
Venue: Meeting room (406), Building 24
Organizer:

SPST


Abstract:  Ferroptosis is a non-apoptotic form of cell death characterized by an overshooting, iron-dependent lipid peroxidation. Ferroptosis is highly relevant not only for a number of degenerative diseases including ischemia/reperfusion injury and neurodegenerative disease, but also represents an attractive target for ferroptosis inducing strategies to combat chemotherapy-resistant tumor entities. Selenocysteine containing glutathione peroxidase (GPX4) is the key regulator of this form of cell death due to its unique activity to scavenge peroxides in lipid bilayers. The role of selenium in form of 21st amino acid selenocysteine has been recently shown to confer full stability towards peroxide-induced irreversible overoxidation and inactivation of GPX4 thereby preventing from ferroptosis in cells and mice. A specific type of inhibitory interneurons in the cortex of newborn mice emerged to require selenium-containing GPX4 thus representing the limiting factor for mammalian life. Recently, genome-wide reverse genetic screens identified acyl-CoA synthetase long-chain family member 4 (ACSL4) as an additional downstream member of the ferroptosis cascade, whose targeted knockout or pharmacological inhibition by thiazolidinediones conferred an unprecedented protection against ferroptosis in cells. In vivo studies are currently being performed to interrogate whether the combined deletion of GPX4 and ACSL4 mitigates tissue damage inflicted by the loss of GPX4 in ferroptosis-sensitive tissues. Moreover, gain-of function studies aim at unravelling yet-unrecognized players in the ferroptosis process. Hence, all these studies are geared towards providing a comprehensive picture whether or not certain ferroptosis players present viable targets for pharmacological intervention to prevent or induce ferroptosis in (neuro)degenerative disease and cancer, respectively.