The Multifaceted Role of the P2X7 Receptor in Alzheimer’s Disease: A Unifying Pathological Link

Abstract:

Alzheimer’s Disease (AD) is a neurodegenerative disorder that characterizes depletion of memory, cognition, and a change in behavioural patterns. There is no standard treatment that completely cures this prevalent disease. This review delves into the existing pathologies of AD, which include the Aβ plaques accumulation, neurofibrillary tangles and Lewy bodies formation, and the influence of the P2X7 receptor on cellular mechanisms of neuronal cells like microglial cells, astrocytes and oligodendrocytes and also its influence on pathways such as JAK2/STAT3, NGF signalling, (Transactive response DNA binding protein) TDP-43 Proteinopathy, Wnt/β-Catenin signalling, and FGF7/FGFR2/PI3K/Akt causing AD. It discusses the unifying role of the P2X7 receptor mediating these pathways that link to the occurrence and progression of AD. The role of the Purinergic receptor (P2X7 receptor), a ligand-gated ion channel activated by extracellular ATP, was examined across existing cellular mechanisms and possible pathways involved in AD, as well as the co-pathologies encompassed and their hypothetical relationship with the P2X7 receptor. Additionally, the current P2X7 receptor antagonists treating neurotoxicity are discussed along with existing pre-clinical and clinical data. This may further advance drug development by targeting the P2X7 receptor to mitigate AD across multiple mechanisms.