Role of P2Y14 receptor modulation in the hippocampal neuroinflammatory responses in in vitro and in vivo models of Alzheimer's Disease

• Grant number: 21/00060-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2021
• End date: November 30, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Alexander Henning Ulrich
• Grantee: Lyvia Lintzmaier Petiz
• 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

Currently, Alzheimer's Disease (AD) is the most prevalent form of dementia, characterized by memory loss, changes in personality and impaired reasoning. Like other neurodegenerative diseases, AD presents a major brain inflammation process at the beginning of its development. This neuroinflammation is known to be triggered by the hyperactivation of glial cells. The persistence of this process causes damage to neurons and results in impaired synaptic transmission and plasticity, which eventually leads to the disorders that characterize this pathology. Recently, in addition to the inflammation caused by hyperactivation of microglia and astrocytes, it has been observed that the recruitment of innate immune cells, such as neutrophils, is also present in AD. A local neuroinflammation promotes an increase in adhesion proteins and factors that lead to the blood-brain barrier rupture, which allows the infiltration of peripheral immune cells. Thus, the study of mechanisms that can prevent such processes are extremely important to avoid AD progress and consequent impairment of neuronal circuits. The P2Y14 receptor, a G protein-coupled purinergic receptor that responds extracellularly to UDP-sugars, is associated with immune and inflammatory processes modulation. Stimulation of this receptor leads to neutrophil chemotaxis and astrocyte activation, confirming that the P2Y14 receptor is an interesting target for studies using neurodegenerative disease models where inflammation plays a critical role. Based on this, the objective of this project is to evaluate the effect of stimulation/inhibition of the P2Y14 receptor on parameters of hippocampal inflammatory responses, using both in vitro and in vivo models of AD. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VILLEGAS, CECILIA; PEREZ, REBECA; PETIZ, LYVIA LINTZMAIER; GLASER, TALITA; ULRICH, HENNING; PAZ, CRISTIAN. Ginkgolides and Huperzine A for complementary treatment of Alzheimer's disease. IUBMB Life, v. 74, n. 8, p. 17-pg., 2022-04-05. (18/08426-0, 18/07366-4, 21/00060-0)