The role of P2X7 and P2Y12 purinergic receptors in the neurodevelopment of autism spectrum disorders and Alzheimer's Disease: Integration of brain organoid and mouse models.

• Grant number: 24/17387-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2025
• End date: April 30, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Alexander Henning Ulrich
• Grantee: Fernanda Tibolla Viero
• 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

Neurodevelopmental disorders, such as autism spectrum disorder (ASD) and Alzheimer's Disease (AD), pose a significant public health challenge due to their high prevalence and the debilitating effects they cause. Fetal neurodevelopment and the early years of life are critical for the formation of neural circuits, neurogenesis, gliogenesis, and synaptic pruning. Consequently, alterations in these processes may predispose individuals to conditions like ASD and AD. The intersection of these disorders suggests that, although they have distinct causes, they may share pathological mechanisms that emerge during neurodevelopment. Recent studies indicate that both ASD and AD may be influenced by disturbances in purinergic signaling, particularly through the P2Y12 and P2X7 receptors, which play crucial roles in neural circuit formation and inflammatory response. This dysregulation may contribute to the pathogenesis of these conditions. However, the roles of these receptors at different stages of neurodevelopment, as well as the underlying mechanisms of these disorders, have yet to be evaluated. Thus, identifying purinergic receptors and altered cellular signaling pathways during neurodevelopment, along with their correlation to AD and ASD, could aid in defining biomarkers for pre-neurodegenerative and symptomatic stages of these diseases. This will facilitate the development of early diagnostic methods and predictions of pathogenicity, as well as identify new therapeutic targets and enhance our understanding of the etiological mechanisms of the disease.