The P2X7 Receptor, a Multifaceted Receptor in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by impaired episodic memory and two pathological lesions: amyloid plaques and neurofibrillary tangles. In AD, damaged neurons and the accumulation of amyloid ß (Aß) peptides cause a significant release of high amounts of extracellular ATP, which acts as a danger signal. The purinergic receptor P2X7 is the main sensor of high concentrations of ATP, and P2X7 has been shown to be upregulated in the brains of AD patients, contributing to the disease's pathological processes. Further, there are many polymorphisms of the P2X7 gene that impact the risk of developing AD. P2X7 can directly modulate Aß plaques and Tau protein lesions as well as the inflammatory response by regulating NLRP3 inflammasome and the expression of several chemokines. The significant role of microglial P2X7 in AD has been well established, although other cell types may also be important in P2X7-mediated mechanisms. In this review, we will discuss the different P2X7-dependent pathways involved in the development of AD.

P2X7-dependent immune pathways in retinal diseases.

Adenosine triphosphate (ATP) is a signalling molecule acting as a neurotransmitter but also as a danger signal. The purinergic receptor P2X7 is the main sensor of high concentration of ATP released by damaged cells. In the eye, P2X7 is expressed by resident microglia and immune cells that infiltrate the retina in disease such as age-related macular degeneration (AMD), a degenerative retinal disease, and uveitis, an inflammatory eye disease. Activation of P2X7 is involved in several physiological and pathological processes: phagocytosis, activation of the inflammasome NLRP3, release of pro-inflammatory mediators and cell death. The aim of this review is to discuss the potential involvement of P2X7 in the development of AMD and uveitis.