Presentation Type
Panel Discussion
Start Date
12-3-2022 1:00 PM
End Date
12-3-2022 2:30 PM
Abstract
Multiple Sclerosis (MS) is a neurodegenerative disease that particularly affects the nerves of the central nervous system (CNS). MS results in the degradation of the myelin sheath surrounding the axon, which is crucial for effective transmission of nerve signals. MS can be detected using lumbar punctures to look for elevated oligoclonal levels and using magnetic resonance imaging (MRI). The MRI can screen for plaques in the CNS, indicating the severity and probability of progression of the disease. Plaques are regions of nerves where the myelin has been removed from the nerves, preventing them from conducting the electrical signals necessary for their proper function. These plaques are associated with inflammation and the accumulation of inflammation-related cells. However, the etiology of MS remains elusive, although the innate immune system is known to play a significant role in disease initiation and progression. The NLRP3 inflammasome, as part of the innate immune system, is one possible initiator of this associated inflammatory response.
The NLRP3 inflammasome is a key component of the canonical pyroptotic pathway, a form of inflammatory cell death that makes use of the protein Gasdermin D. The N-terminus of Gasdermin D is able to form a transmembrane pore through which cytokines are released, resulting in cell death. Testing of the mechanism of a new MS treatment, dimethyl fumarate, revealed that the treatment causes succination in such a way that access to Gasdermin D by Caspase 1 is blocked, inhibiting pyroptosis and the associated inflammation.
To see a recording of the presentation: https://youtu.be/2aPWlijOoEY.
Keywords
Multiple Sclerosis, Gasdermin D, NLRP3 Inflammasome, Caspase 1, Pyroptosis, Dimethyl Fumarate
Included in
A Brief Discussion of Gasdermin D's Function in Multiple Sclerosis
Multiple Sclerosis (MS) is a neurodegenerative disease that particularly affects the nerves of the central nervous system (CNS). MS results in the degradation of the myelin sheath surrounding the axon, which is crucial for effective transmission of nerve signals. MS can be detected using lumbar punctures to look for elevated oligoclonal levels and using magnetic resonance imaging (MRI). The MRI can screen for plaques in the CNS, indicating the severity and probability of progression of the disease. Plaques are regions of nerves where the myelin has been removed from the nerves, preventing them from conducting the electrical signals necessary for their proper function. These plaques are associated with inflammation and the accumulation of inflammation-related cells. However, the etiology of MS remains elusive, although the innate immune system is known to play a significant role in disease initiation and progression. The NLRP3 inflammasome, as part of the innate immune system, is one possible initiator of this associated inflammatory response.
The NLRP3 inflammasome is a key component of the canonical pyroptotic pathway, a form of inflammatory cell death that makes use of the protein Gasdermin D. The N-terminus of Gasdermin D is able to form a transmembrane pore through which cytokines are released, resulting in cell death. Testing of the mechanism of a new MS treatment, dimethyl fumarate, revealed that the treatment causes succination in such a way that access to Gasdermin D by Caspase 1 is blocked, inhibiting pyroptosis and the associated inflammation.
To see a recording of the presentation: https://youtu.be/2aPWlijOoEY.