Role of the P2X7 purinergic receptor in microglia-mediated neurotoxicity in models of Alzheimer's disease and its possible correlation with the modulation of neurogenesis

• Grant number: 22/12888-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2022
• End date: October 31, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Alexander Henning Ulrich
• Grantee: Guilherme de Azevedo Carvalho
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases, AP.TEM

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease whose incidence tends to increasewith the increase in the life expectancy of the world population, constituting the main form ofdementia among the elderly. To date, there are no effective therapeutic alternatives for thisillness. Beta-amyloid peptide oligomers (ABOs) are considered the mainneurotoxins involved in several deleterious events characteristic of the disease, such asoxidative stress, mitochondrial and synaptic dysfunction, tau protein hyperphosphorylation,changes in calcium homeostasis and activation of microglia and astrocytes, in addition to generating deficitsin recognition memory and depressive behavior. Several evidences have shown that inflammation plays a relevant role in AD, as well as in the modulation of neurogenesis. Interestingly, there appears to be a significant influence of microgliain both processes. However, there is still no consensus on how tothis occurs. On the other hand, a study demonstrated that the activation of microglia by the beta-amyloid (AB), requires the expression of P2X7R, and is also associated with the release of IL-1beta by these cells. P2X7R activation in microglia was also associated with neuronal damage in co-culture models, whereas silencing of these receptors increased AB phagocytosis by microglia.