Alzheimer's disease (AD) is the most common cause of dementia in the general population and, to date, constitutes a major therapeutic challenge. In the pathogenesis of AD, aggregates of amyloid β (Aβ) and neurofibrillary tangles (NFTs) containing Tau-microtubule-associated protein (tau) are known to trigger a neuroinflammatory response with subsequent formation of an inflammasome. In particular, the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is thought to play a crucial role in AD-related pathology. While the mechanisms for NLRP3 activation are not fully understood, it has been demonstrated that, after detection of protein aggregates, NLRP3 induces pro-inflammatory cytokines, such as interleukin 18 (IL-18) or interleukin 1β (IL-1β), that further potentiate AD progression. Specific inhibitors of NLRP3 that exhibit various mechanisms to attenuate the activity of NLRP3 have been tested in in vivo studies and have yielded promising results, as shown by the reduced level of tau and Aβ aggregates and diminished cognitive impairment. Herein, we would like to summarize the current state of knowledge on NLRP3 inflammasome priming, activation, and its actual role in AD pathogenesis, and to characterize the NLRP3 inhibitors that have been studied most and their impact on AD-related pathology.
Keywords: Alzheimer’s disease; Alzheimer’s disease treatment; NOD-like receptor pyrin domain-containing 3; NOD-like receptor pyrin domain-containing 3 inflammasome; NOD-like receptor pyrin domain-containing 3 inhibitors; amyloid β; neurofibrillary tangles.