Is Targeting the Inflammasome a Way Forward for Neuroscience Drug Discovery?
In the December 2018 issue of SLAS Discovery, researchers from the University of Manchester (United Kingdom) explore recent developments and strategies for targeting the NLRP3 inflammasome as a potential therapeutic target in acute and chronic neurological and neurodegenerative diseases, and offer perspective on how this field may develop in the future.
The progression and development of both acute and chronic neurological and neurodegenerative conditions, such as stroke or Alzheimer’s disease, are now recognized to involve the host inflammatory response. That is to say, a body’s own immune system reacts to the disease, but ultimately makes things worse, not better. Recent research now suggests that a specific component of the inflammatory response may be largely responsible for the worsening of disease. Inflammatory cells in the brain, called microglia, contain a protein called NLRP3. The job of NLRP3 is to sense for alterations in cellular homeostasis, and when the cell is sufficiently perturbed, NLRP3 undergoes an oligomerisation process with other proteins in the cell to form a macromolecular complex inside the cell called the inflammasome. Once active, the inflammasome complex catalyses activation and secretion of pro-inflammatory molecules that then cause inflammation in the tissue environment. In the brain this is devastating.
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