Role of NLRP3 Inflammasome and Its Inhibitors as Emerging Therapeutic Drug Candidate for Alzheimer's Disease: a Review of Mechanism of Activation, Regulation, and Inhibition

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. The etiology and pathology of AD are complicated, variable, and yet to be completely discovered. However, the involvement of inflammasomes, particularly the NLRP3 inflammasome, has been emphasized recently. NLRP3 is a critical pattern recognition receptor involved in the expression of immune responses and has been found to play a significant role in the development of various immunological and neurological disorders such as multiple sclerosis, ulcerative colitis, gout, diabetes, and AD. It is a multimeric protein which releases various cytokines and causes caspase-1 activation through the process known as pyroptosis. Increased levels of cytokines (IL-1 beta and IL-18), caspase-1 activation, and neuropathogenic stimulus lead to the formation of proinflammatory microglial M1. Progressive researches have also shown that besides loss of neurons, the pathophysiology of AD primarily includes amyloid beta (A beta) accumulation, generation of oxidative stress, and microglial damage leading to activation of NLRP3 inflammasome that eventually leads to neuroinflammation and dementia. It has been suggested in the literature that suppressing the activity of the NLRP3 inflammasome has substantial potential to prevent, manage, and treat Alzheimer's disease. The present review discusses the functional composition, various models, signaling molecules, pathways, and evidence of NLRP3 activation in AD. The manuscript also discusses the synthetic drugs, their clinical status, and projected natural products as a potential therapeutic approach to manage and treat NLRP3 mediated AD.

Automated summary

Alzheimer's disease is a complex neurodegenerative disorder with unclear etiology and pathology. Recent research has highlighted the involvement of inflammasomes, particularly the NLRP3 inflammasome, in the disease. NLRP3 is a critical receptor involved in immune responses and has been found to play a significant role in various immunological and neurological disorders. Inhibiting the activity of the NLRP3 inflammasome has been suggested as a promising approach for preventing and treating Alzheimer's disease.