Mitochondrial ROS promotes susceptibility to infection via gasdermin D-mediated necroptosis

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• The road ahead: 2022 January 20, 2022 # # # # The first post at the start of each year on the SoPD website tries to provide an overview of where things are in the search for ‘disease modifying’ therapies for Parkinson’s.  It is an exercise in managing expectations as well as discussing what research events are scheduled for the next year so that we can keep…
• The road ahead: 2021 January 25, 2021 # # # # At the start of each year, it is a useful practise to layout what is planned over the next 12 months. The events that are scheduled for the year to come, so that we can keep an eye out for them. Obviously, where 2021 will end actually is unpredictable, but an outline of what is scheduled…
• Mitochondrial ROS promotes susceptibility to infection via gasdermin D-mediated necroptosis July 30, 2022 Cell. 2022 Jul 29:S0092-8674(22)00790-5. doi: 10.1016/j.cell.2022.06.038. Online ahead of print.ABSTRACTAlthough mutations in mitochondrial-associated genes are linked to inflammation and susceptibility to infection, their mechanistic contributions to immune outcomes remain ill-defined. We discovered that the disease-associated gain-of-function allele Lrrk2G2019S (leucine-rich repeat kinase 2) perturbs mitochondrial homeostasis and reprograms cell death pathways in macrophages. When the inflammasome is activated in Lrrk2G2019S macrophages,…
• Mitochondrial ROS promotes susceptibility to infection via gasdermin D-mediated necroptosis July 30, 2022 Cell. 2022 Jul 29:S0092-8674(22)00790-5. doi: 10.1016/j.cell.2022.06.038. Online ahead of print.ABSTRACTAlthough mutations in mitochondrial-associated genes are linked to inflammation and susceptibility to infection, their mechanistic contributions to immune outcomes remain ill-defined. We discovered that the disease-associated gain-of-function allele Lrrk2G2019S (leucine-rich repeat kinase 2) perturbs mitochondrial homeostasis and reprograms cell death pathways in macrophages. When the inflammasome is activated in Lrrk2G2019S macrophages,…
• Mitochondrial ROS promotes susceptibility to infection via gasdermin D-mediated necroptosis July 30, 2022 Cell. 2022 Jul 29:S0092-8674(22)00790-5. doi: 10.1016/j.cell.2022.06.038. Online ahead of print.ABSTRACTAlthough mutations in mitochondrial-associated genes are linked to inflammation and susceptibility to infection, their mechanistic contributions to immune outcomes remain ill-defined. We discovered that the disease-associated gain-of-function allele Lrrk2G2019S (leucine-rich repeat kinase 2) perturbs mitochondrial homeostasis and reprograms cell death pathways in macrophages. When the inflammasome is activated in Lrrk2G2019S macrophages,…
• Mitochondrial ROS promotes susceptibility to infection via gasdermin D-mediated necroptosis July 30, 2022 Cell. 2022 Jul 29:S0092-8674(22)00790-5. doi: 10.1016/j.cell.2022.06.038. Online ahead of print.ABSTRACTAlthough mutations in mitochondrial-associated genes are linked to inflammation and susceptibility to infection, their mechanistic contributions to immune outcomes remain ill-defined. We discovered that the disease-associated gain-of-function allele Lrrk2G2019S (leucine-rich repeat kinase 2) perturbs mitochondrial homeostasis and reprograms cell death pathways in macrophages. When the inflammasome is activated in Lrrk2G2019S macrophages,…
• Mitochondrial ROS promotes susceptibility to infection via gasdermin D-mediated necroptosis July 30, 2022 Cell. 2022 Jul 29:S0092-8674(22)00790-5. doi: 10.1016/j.cell.2022.06.038. Online ahead of print.ABSTRACTAlthough mutations in mitochondrial-associated genes are linked to inflammation and susceptibility to infection, their mechanistic contributions to immune outcomes remain ill-defined. We discovered that the disease-associated gain-of-function allele Lrrk2G2019S (leucine-rich repeat kinase 2) perturbs mitochondrial homeostasis and reprograms cell death pathways in macrophages. When the inflammasome is activated in Lrrk2G2019S macrophages,…
• Denali’s Phase I results May 27, 2021 # # # # Leucine-rich repeat kinase 2 (or LRRK2) is a large, multi function protein that is associated with Parkinson’s. People with genetic variations in the region of DNA that provides the instructions for making LRRK2 protein have a higher risk of developing the condition. In many cases of Parkinson’s, LRRK2 can become hyperactive. Researchers and biotech companies have…
• 2019: Year in review December 31, 2019   In this end-of-year post, we review the Parkinson’s research that caught our attention at SoPD HQ in 2019. Month-by-month we will briefly discuss some of the major pieces of research/announcements that have defined the year and advanced our understanding of Parkinson’s. The list is based on nothing more than the author’s personal opinion – apologies to any researchers who…
• The luminance of a lighthouse January 24, 2022 # # # # LRRK2 inhibition represents one of several biological approaches to slowing the progression of Parkinson’s that is currently being clinically tested. Leading the charge in the development of LRRK2 inhibitors is a biotech company called Denali Therapeutics (in partnership with Biogen). Recently, the company provided news on the immediate future clinical development plans for their lead molecule…
• The road ahead: 2020 January 5, 2020 Here at the SoPD, we are primarily interested in disease modification for Parkinson’s. While there is a great deal of interesting research exploring the causes of the condition, novel symptomatic therapies, and other aspects of Parkinson’s, my focus is generally on the science seeking to slow, stop or reverse the condition. At the start of each year, it is a…
• Monthly research review – March 2021 March 31, 2021 # # # # At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during March 2021. The post is divided into ten parts based on the type of research: Top 5 pieces of Parkinson’s news Articles of general interest Basic biology…
• The inflammasome field is heating up December 6, 2019   When a cell is sick or damaged it will send out signals alerting the immune system that something is wrong. If enough of these molecules are released, they will initate an “immune response” and this process is called inflammation. There is evidence in neurodegenerative conditions (like Parkinson’s and Alzheimer’s) that the inflammation process is involved, and inhibitors of particular…
• Monthly research review: February 2020 February 29, 2020   At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during February 2020. The post is divided into seven parts based on the type of research: Basic biology Disease mechanism Clinical research New clinical trials Clinical trial news Other news Review…
• The Llama-nation of LRRK2 April 8, 2022 # # # # Antibodies are tiny y-shaped markers used by the immune system to label foreign agents within the body. Once bound to something, antibodies can alert immune cells to come and remove the object. Antibodies can also inhibit the object from doing anything nasty, like infecting or damaging a cell. Between species, different types of antibodies have been…
• Monthly research review – October 2019 October 31, 2019   At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during October 2019. The post is divided into seven parts based on the type of research: Basic biology Disease mechanism Clinical research New clinical trials Clinical trial news Other news Review…
• Something LRRKing in the immune system October 12, 2019     Canadian scientists recently reported that mice with a specific genetic variation – in the Parkinson’s-associated LRRK2 gene – differ in how they are able to deal with bacterial and viral infections. Curiously, mice with the Parkinson’s-associated LRRK2 mutation could handle a bacterial infection better than normal mice, while mice with no LRRK2 protein struggled against the infection. And…
• Monthly Research Review – February 2021 February 28, 2021 # # # # At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during February 2021. The post is divided into eight parts based on the type of research: Basic biology Disease mechanism Clinical research New clinical trials Clinical trial news…
• Monthly Research Review – July 2021 July 31, 2021 # # # # At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during July 2021. The post is divided into 10 parts based on the type of research: Top 5 pieces of Parkinson’s news Articles of general interest Basic biology…
• Monthly Research Review: January 2022 January 31, 2022 # # # # At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during January 2022. The post is divided into 10 parts based on the type of research: Top 6 pieces of Parkinson’s news Articles of general interest Basic biology…
• Monthly Research Review – September 2019 September 30, 2019   At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during September 2019. The post is divided into seven parts based on the type of research: Basic biology Disease mechanism Clinical research New clinical trials Clinical trial news Other news Review…
• Monthly Research Review – September 2021 September 30, 2021 # # # # At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during September 2021. The post is divided into 10 parts based on the type of research: Top 4 pieces of Parkinson’s news Articles of general interest Basic biology…