P2X7 Receptor: an Emerging Target in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a major cause of age-related dementia, which is becoming a global health crisis. However, the pathogenesis and etiology of AD are still not fully understood. And there are no valid treatment methods or precise diagnostic tools for AD. There is increasing evidence that P2X7R expression is upregulated in AD and is involved in multiple related pathological processes such as Aβ plaques, neurogenic fiber tangles, oxidative stress, and chronic neuroinflammation. This suggests that P2X7R may be a key player in the development of AD. P2X7R is a member of the ligand-gated purinergic receptor (P2X) family. It has received attention in neuroscience due to its role in a wide range of aging and age-related neurological disorders. In this review, we summarize current information on the roles of P2X7R in AD and suggest potential pharmacological interventions to slow down AD progression.

The emerging role of brain neuroinflammatory responses in Alzheimer’s disease

“…Nicodipine (P2X7R antagonists), a dihydropyridine calcium channel antagonist, has also been shown to confer neuroprotective effects by reducing the levels of activated NF-κB and inhibiting the release of mature IL-1β in Aβ-stimulated microglia (whose potential target is P2X7R), which plays a permissive role in NLRP3 inflammasome activation and cytokines release ( Ryu and McLarnon, 2008 ; Di Virgilio et al, 2017 ; Huang et al, 2023 ). The list of recent agents for treatment strategy of AD is provided in Table 3 .…”

The neuroinflammatory role of microglia in Alzheimer's disease and their associated therapeutic targets

“…According to an in vivo study, minocycline inhibits the NLRP3 inflammasome, which lowers Aβ accumulation and attenuates microglial activation 139,140 . As a dihydropyridine calcium channel antagonist, nicodipine (P2X7R antagonists) has also been demonstrated to provide neuroprotective effects by lowering activated NF‐κB levels and preventing the release of mature IL‐1β in Aβ‐stimulated microglia (whose possible target is P2X7R), which is permissive in NLRP3 inflammasome activation and cytokine synthesis 141–143 . To the best of our knowledge, we highlighted all the agents for therapeutic strategies in AD in Table 3.…”