New therapeutic approach of the Parkinson´s disease: Neuroprotection stimulated by pharmacological modulation of the intracellular signaling by Ca2+/cAMP/NO

• Grant number: 17/25565-1
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2018
• End date: November 30, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Afonso Caricati Neto
• Grantee: Afonso Caricati Neto
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Abstract - Characterized by severe motor dysfunctions resulting from the degeneration and death of dopaminergic (DA) neurons mainly from the substantia nigra (SN), Parkinson's disease (PD) is the second most common neurodegenerative disorder in developed countries. There is no cure or proven strategy for slowing the progression of this disease. Although the pathophysiological mechanisms of PD remain under investigation, there is little doubt of the involvement of cytosolic Ca2+ overload consequent to imbalance in intracellular Ca2+ homeostasis in the degeneration and death of DA neurons. Thus, the pharmacological modulation of intracellular Ca2+ signaling to attenuate the degeneration and death of DA neurons has become a promising neuroprotective strategy in PD therapy. Recent studies from our laboratory have shown that several cellular responses, such as neurotransmitter release and cellular survival, are regulated by the interaction of Ca2+ with other intracellular messenger systems, such as cyclic adenosine monophosphate (cAMP) and nitric oxide (NO), thus establishing a functional interaction of Ca2+/cAMP/NO intracellular signaling. In this way, we have proposed that the pharmacological modulation of this Ca2+/cAMP/NO signaling could importantly contribute to the development of new therapeutic strategies of neurodegenerative diseases, including PD. Based on this proposal, this research project aims to evaluate the neuroprotective effect stimulated by the pharmacological modulation of Ca2+/cAMP/NO intracellular signaling in animal model of PD. (AU)

Scientific publications

(8)

(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)

MENEZES-RODRIGUES, FRANCISCO SANDRO; ERRANTE, PAOLO RUGGERO; ARAUJO, ERISVALDO AMARANTE; PACHECO FERNANDES, MARIANA PONTES; DA SILVA, MICHELE MENDES; PIRES-OLIVEIRA, MARCELO; SCORZA, CARLA ALESSANDRA; SCORZA, FULVIO ALEXANDRE; TAHA, MURCHED OMAR; CARICATI-NETO, AFONSO. Cardioprotection stimulated by resveratrol and grape products prevents lethal cardiac arrhythmias in an animal model of ischemia and reperfusion. Acta Cirurgica Brasileira, v. 36, n. 3, 2021. (17/25565-1)

GLEIDE GATTI FONTES; RODRIGO DE BARROS FREITAS; PALLOMA PORTO ALMEIDA; LUCIANA MOREIRA LIMA; SILVIA ALMEIDA CARDOSO; VIRGINIA RAMOS PIZZIOLO; RICARDO TABACH; ALMIR GONÇALVES WANDERLEY; RICARDO MARIO ARIDA; AFONSO CARICATI-NETO; et al. Effects of Calendula officinalis extract on liver histopathology, lipid profile, and oxidative stress in rats submitted to a diet rich in cholesterol and carbohydrates. Acta Cirurgica Brasileira, v. 38, 2023-10-13. (22/10696-1, 17/25565-1)

BRAGA FILHO, CARLOS EDUARDO; PEREIRA BARBOSA, ADRIANO HENRIQUE; DUARTE NICOLAU, LUCAS ANTONIO; ROLIM MEDEIROS, JAND VENES; PIRES-OLIVEIRA, MARCELO; DOS SANTOS POVOA, RUI MANUEL; PENARANDA GOVATO, TANIA CARMEN; FERNANDES FERNANDES JUNIOR, HEZIO JADIR; DE CARVALHO, RAFAEL GUZELLA; LUNA-FILHO, BRAULIO; et al. Pharmacological Modulation by Low Molecular Weight Heparin of Purinergic Signaling in Cardiac Cells Prevents Arrhythmia and Lethality Induced by Myocardial Infarction. JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE, v. 10, n. 3, p. 13-pg., 2023-03-01. (17/25565-1)

FÚLVIO ALEXANDRE SCORZA; FRANCISCO SANDRO MENEZES-RODRIGUES; EFRAÍN OLSZEWER; PAOLO RUGGERO ERRANTE; JOSÉ GUSTAVO PATRÃO TAVARES; CARLA ALESSANDRA SCORZA; HENRIQUE BALLALAI FERRAZ; JOSEF FINSTERER; AFONSO CARICATI-NETO. The mitochondrial calcium uniporter: a new therapeutic target for Parkinson’s disease-related cardiac dysfunctions?. Clinics, v. 75, 2020-01-10. (16/06879-2, 17/25565-1)

FRANCISCO SANDRO MENEZES-RODRIGUES; JOSÉ GUSTAVO PADRÃO TAVARES; ENIO RODRIGUES VASQUES; PAOLO RUGGERO ERRANTE; ERISVALDO AMARANTE DE ARAÚJO; MARCELO PIRES-OLIVEIRA; CARLA ALESSANDRA SCORZA; FÚLVIO ALEXANDRE SCORZA; MURCHED OMAR TAHA; AFONSO CARICATI-NETO. Cardioprotective effects of pharmacological blockade of the mitochondrial calcium uniporter on myocardial ischemia-reperfusion injury. Acta Cirurgica Brasileira, v. 35, n. 3, 2020-05-20. (17/25565-1)

CARICATI-NETO, AFONSO; ERRANTE, PAOLO RUGGERO; MENEZES-RODRIGUES, FRANCISCO SANDRO. Recent Advances in Pharmacological and Non-Pharmacological Strategies of Cardioprotection. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 16, AUG 2 2019. (17/25565-1)

FRANCISCO SANDRO MENEZES-RODRIGUES; MARCELO PIRES DE OLIVEIRA; ERISVALDO AMARANTE ARAÚJO; HENRIQUE BALLALAI FERRAZ; JOSEF FINSTERER; EFRAIN OLSZEWER; MURCHED OMAR TAHA; CARLA ALESSANDRA SCORZA; AFONSO CARICATI-NETO; FÚLVIO ALEXANDRE SCORZA. Role of cardiac β1-adrenergic and A1-adenosine receptors in severe arrhythmias related to Parkinson's disease. Clinics, v. 78, 2023-09-01. (18/18568-7, 17/25565-1)

SCORZA, FULVIO ALEXANDRE; MENEZES-RODRIGUES, FRANCISCO SANDRO; OLSZEWER, EFRAIN; ERRANTE, PAOLO RUGGERO; PATRAO TAVARES, JOSE PRIME GUSTAVO; SCORZA, CARLA ALESSANDRA; FERRAZ, HENRIQUE BALLALAI; FINSTERER, JOSEF; CARICATI-NETO, AFONSO. The mitochondrial calcium uniporter: a new therapeutic target for Parkinson's disease-related cardiac dysfunctions?. Clinics, v. 75, p. 5-pg., 2020-01-01. (17/25565-1, 16/06879-2)