Potential Benefits of Quercetin through P2X7 Modulation against Neuroinflammation in Alzheimer's Disease

Alzheimer's disease is the leading cause of dementia worldwide. It belongs to the group of neurodegenerative ailments caused by the accumulation of extracellular β-amyloid plaques (Aβ) and intracellular neurofibrillary tau tangles, which damage brain tissue. One of the mechanisms proposed involves protein neurotoxicity and neuroinflammation through the purinergic system pathway. Several endogenous nucleotides, such as Adenosine 5'-triphosphate (ATP), are involved in cell signaling. High ATP levels can cause P2X7 receptor hyper-stimulation, resulting in an exacerbated inflammatory process and in apoptosis of cells. From this perspective, searching for new therapies becomes important to assist in the patient's treatment and quality of life. As a flavonoid with several properties, including anti-inflammatory activity, Quercetin may be an alternative to alleviate the damage and symptoms caused by Alzheimer's disease. Therefore, this review aims to examine the potential of Quercetin through P2X7 modulation against neuroinflammation in Alzheimer's disease, as it affects the P2X7 receptor by direct and indirect interactions, resulting in decreased inflammation levels. Therefore, we believe that Quercetin may have significant power in modulating the P2X7 receptor, demonstrating that the purinergic system has the potential to modulate neuroinflammation and can add to the treatment, reduce disease progression, and result in better prognoses. Furthermore, technological alternatives such as Quercetin micronization might improve its delivery to target tissues.