• During aging, the central nervous system (“CNS”) becomes more inflammatory, leading to activation of microglia (“CNS immune cells”), tissue damage, dysfunction, and senescence
• The article reviews microglial pathways, including the NLRP3 inflammasome pathway, which are promising drug targets for potential treatment of Alzheimer’s disease (“AD”) and slowing of cognitive aging

In the paper titled, “Microglia: A pharmacological target for the treatment of age-related cognitive decline and Alzheimer’s disease,” the authors reviewed data associated with microglial pathways that have potential as drug targets for treatment of MCI and AD. Reported data supporting the NLRP3 inflammasome pathway as a drug target are summarized below:

• IL-1β, which is considered toxic to microglia by triggering increased oxidative stress and apoptosis (“cell death”), is elevated in cerebrospinal fluid and brains of patients with AD
• IC 100, an anti-ASC antibody which permeates the blood-brain-barrier and binds to ASC filaments, blocks IL-1β production in human whole blood cell assays
• Inflammasome ASC, which is produced by microglia, binds to amyloid beta (“Aβ”) and aids in formation of Aβ oligomers - administration of an anti-ASC antibody in an AD mouse model prevented Aβ from accumulating
• AD mouse models deficient in NLRP3 or caspase-1 demonstrate reduced activation of IL-1β and reduced spatial memory loss
• Administration of a caspase-1 inhibitor in a mouse model of “Aβ” pathology reversed impairment of episodic and spatial memory, while preventing brain inflammation and Aβ build up
• Administration of a compound that inhibits NLRP3 assembly, reduced levels of IL-1β and Aβ which were associated with improved working and recognition memory in an AD mouse model; this compound administered to a Tau-P301S mouse model of AD prevented Tau pathology

The authors stated, “thus far, animal models testing NLRP3 pathway inhibitors suggest that such treatments may have pharmacologic relevance in reducing cognitive aging and AD pathology within patients.” To read the article Click Here.

“There is a tremendous unmet need to identify effective therapies to treat the growing number of people with cognitive impairment and Alzheimer’s disease, a leading cause of disability and death in the world,” stated Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO, and President. “It is encouraging to see the extensive research underway to identify potential drug targets. We are proud of the original scientific contributions in this area by the inventors of ZyVersa’s Inflammasome ASC Inhibitor IC 100, Drs. Robert W. Keane and Juan Pablo de Rivero Vaccari at the University of Miami Miller School of Medicine.” To review their latest publication on Alzheimer’s disease, Click Here.