Impairment in the expression/function of the alpha7 nicotinic cholinergic receptor: mechanisms and implications for diseases associated with inflammatory processes

• Grant number: 23/11144-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: December 01, 2024
• End date: November 30, 2029
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcio Alberto Torsoni
• Grantee: Marcio Alberto Torsoni
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Pesquisadores principais: Adriana Souza Torsoni
• Associated researchers: Fernando Moreira Simabuco ; Laís Angélica de Paula Simino ; Letícia Ignácio de Souza Zimmermann ; Marciane Milanski Ferreira ; Mina Harshadbhai Desai ; Penélope Lacrísio dos Reis Menta

Abstract

Numerous diseases, in which the inflammatory process plays an important role in pathophysiology, have a high prevalence in the population, such as obesity, diabetes, cardiovascular diseases, cancer, and inflammatory bowel diseases. The immune system utilizes inflammatory processes to act against infectious agents, but excessive activation can have consequences for the organism. The alpha7 nicotinic cholinergic receptor (alpha7nAChR), in addition to its function as an ion channel, participates in this control by inhibiting cytokine expression through the activation of JAK2/STAT3 proteins and other cellular signaling pathways. Therefore, this receptor has great potential to participate in the prevention/treatment of certain pathologies in which the inflammatory process worsens the disease. Paradoxically, in some inflammatory conditions (obesity, sepsis, and consumption of a high-fat diet), the hypothalamic expression of the ±7nAChR is impaired, but in other conditions, its expression is increased, for example, in some types of cancer. To date, no study has investigated the mechanisms involved in the impairment of alpha7nAChR expression, the relationship of this event with the consumption of a high-fat diet, weight gain, and the course of colitis and cancer. Our studies have shown that the loss of the receptor in the hypothalamus is an early process, but the responsible mechanism(s) is (are) still unknown. This proposal aims to investigate the mechanisms that may cause impairment of receptor expression in the hypothalamus and intestine, as well as the role of this receptor in neurogenesis, colitis, and cancer. The data obtained may advance our knowledge in molecular biology, by identifying the mechanism, as well as identifying a new target for the prevention and treatment of the investigated pathologies. (AU)