Autophagy modulation by cannabinoids: neuroprotection in Parkinson's Disease

• Grant number: 19/02821-8
• Support Opportunities: Research Projects - Thematic Grants
• Start date: February 01, 2020
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Soraya Soubhi Smaili
• Grantee: Soraya Soubhi Smaili
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Carlos Eduardo Neves Girardi ; Claudia Bincoletto Trindade ; Fabio Cardoso Cruz ; Gustavo José da Silva Pereira ; Regina Helena da Silva ; Rodrigo Portes Ureshino ; Vanessa Costhek Abílio
• Associated research grant(s): 22/04154-1 - Multi-User equipament approved : Fluorescence Microscope Leica THUNDER Imager 3D Assay, AP.EMU
• Associated scholarship(s): 24/00686-4 - DIALOGUE ON CANNABINOIDS IN MEDICINE, BP.JC; 24/02909-0 - Implementation of Zebrafish Experimental Model for the Study of Cannabinoids and Other Drugs, BP.TT; 24/00659-7 - Dialogue about cannabinoids in the treatment of diseases, BP.JC; 20/08840-1 - Study of autophagy and neuroprotection mediated by cannabinoids compounds in vitro and in vivo models of Parkinson's Disease, BP.PD

Abstract

The process of macroautophagia (autophagy) has been the focus of studies on various topics such as neurodegeneration, immune system, inflammation and cancer. In this way, understanding the molecular and cellular mechanisms that modulate aautophagy utophagy is fundamental. In fact, these studies may help in the identification of important targets for the development of new drugs and therapies. In progressive neurodegenerative disorders, long-term or cure treatments are not yet available. At the same time, these have gained relevance with the increasing aging of the world population. It is known that autophagy is capable of promoting the improvement of toxicity induced by the accumulation of alpha-synuclein, but may also contribute to the elimination of malformed proteins. Many authors have presented concrete evidence of autophagic action in neuroprotection and research safe tools to induce it in patients. Parkinson's disease (PD) is the second most prevalent age-related neurodegenerative disease. Evidence shows that there is a correlation between changes in autophagic processes and PD. In this sense, the accumulation of alpha-synuclein protein aggregates (Lewy bodies, the main pathological marker of PD) has been shown to reduce autophagy, aggravating PD-related neurodegenerative processes. Cannabinoid substances such as delta-9-THC and cannabidiol have shown neuroprotective potential and in vitro studies suggest a beneficial effect on neurodegeneration underlying PD. Preliminary data from our laboratories indicate that cannabidiol may have a pro-autophagic effect which reduces behavioral alterations related to PD. However, the mechanisms of the relationship between cannabidiol, autophagy and PD need to be studied. Thus, the aim of this project will be to investigate the role of cannabinoids as potential modulators of autophagy in vitro and in vivo models of PD. The neuroprotective effects of different cannabinoids will be studied. In addition, the induction and modulation of autophagic signaling pathways and their ability to promote neuroprotection will be investigated and translated to studies in patients. (AU)

Scientific publications

(9)

(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)

PEREIRA, GUSTAVO JOSE DA SILVA; LEAO, ANDERSON HENRIQUE FRANCA FIGUEREDO; ERUSTES, ADOLFO GARCIA; MORAIS, INGRID BEATRIZ DE MELO; VRECHI, TALITA APARECIDA DE MORAES; ZAMARIOLI, LUCAS DOS SANTOS; PEREIRA, CASSIA ARRUDA SOUZA; MARCHIORO, LAIS DE OLIVEIRA; SPERANDIO, LETICIA PAULINO; LINS, ISIS VALESKA FREIRE; et al. Pharmacological Modulators of Autophagy as a Potential Strategy for the Treatment of COVID-19. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 8, APR 2021. (19/14722-4, 17/10863-7, 19/02821-8)

SPERANDIO, LETICIA PAULINO; LINS, ISIS VALESKA F.; ERUSTES, ADOLFO G.; LEAO, ANDERSON H. F. F.; ANTUNES, FERNANDA; MORAIS, INGRID B. M.; VIEIRA, HERON FERNANDES; DE CAMPOS, LAIS MARIA; BINCOLETTO, CLAUDIA; SMAILI, SORAYA S.; et al. Blocking Autophagy by the Two-Pore Channels Antagonist Tetrandrine Improves Sorafenib-Induced Death of Hepatocellular Carcinoma Cells. TOXICOLOGY IN VITRO, v. 90, p. 11-pg., 2023-05-12. (19/14722-4, 17/10863-7, 19/02821-8)

NASCIMENTO, ANA CAROLINA; ERUSTES, ADOLFO G.; RECKZIEGEL, PATRICIA; BINCOLETTO, CLAUDIA; URESHINO, RODRIGO P.; PEREIRA, GUSTAVO J. S.; SMAILI, SORAYA S.. alpha-Synuclein Overexpression Induces Lysosomal Dysfunction and Autophagy Impairment in Human Neuroblastoma SH-SY5Y. Neurochemical Research, v. 45, n. 11, p. 13-pg., 2020-09-11. (13/20073-2, 19/02821-8, 17/10863-7, 16/20796-2)

ERUSTES, ADOLFO G.; ABILIO, VANESSA C.; BINCOLETTO, CLAUDIA; PIACENTINI, MAURO; PEREIRA, GUSTAVO J. S.; SMAILI, SORAYA S.. Cannabidiol induces autophagy via CB₁ receptor and reduces α-synuclein cytosolic levels. Brain Research, v. 1850, p. 10-pg., 2024-12-24. (19/02821-8, 19/14722-4, 13/20073-2, 20/08840-1, 17/10863-7)

FLORENTINO, PILAR TAVARES VERAS; ARAUJO, VINICIUS DE OLIVEIRA; ZATTI, HENRIQUE; LUIS, CAIO VINICIUS; CAVALCANTI, CELIA REGINA SANTOS; DE OLIVEIRA, MATHEUS HENRIQUE CITIBALDI; LEAO, ANDERSON HENRIQUE FRANCA FIGUEREDO; BERTOLDO JUNIOR, JURACY; BARBOSA, GEORGE G. CAIQUE; RAVERA, ERNESTO; et al. Text mining method to unravel long COVID's clinical condition in hospitalized patients. CELL DEATH & DISEASE, v. 15, n. 9, p. 9-pg., 2024-09-13. (19/02821-8)

COSTA, ANGELICA JARDIM; OLIVEIRA, RAFAELA BRITO; WACHILEWSKI, PATRICIA; NISHINO, MICHELLE SAYURI; BASSANI, TAYSA BERVIAN; STILHANO, ROBERTA SESSA; CERUTTI, JANETE MARIA; NOZIMA, BRUNO; PORTO, CATARINA SEGRETI; DA SILVA PEREIRA, GUSTAVO JOSE; et al. Membrane estrogen receptor ERa activation improves tau clearance via autophagy induction in a tauopathy cell model. Brain Research, v. 1795, p. 16-pg., 2022-09-13. (19/02821-8, 20/04709-8, 19/14722-4, 16/20796-2, 17/23616-8, 17/10863-7, 18/16719-8, 18/02762-9)

NASCIMENTO, ANA CAROLINA; ERUSTES, ADOLFO G.; RECKZIEGEL, PATRICIA; BINCOLETTO, CLAUDIA; URESHINO, RODRIGO P.; PEREIRA, GUSTAVO J. S.; SMAILI, SORAYA S.. alpha-Synuclein Overexpression Induces Lysosomal Dysfunction and Autophagy Impairment in Human Neuroblastoma SH-SY5Y. Neurochemical Research, SEP 2020. (19/02821-8, 16/20796-2, 13/20073-2, 17/10863-7)

VRECHI, TALITA A. M.; LEAO, ANDERSON H. F. F.; MORAIS, INGRID B. M.; ABILIO, VANESSA C.; ZUARDI, ANTONIO W.; HALLAK, JAIME EDUARDO C.; CRIPPA, JOSE ALEXANDRE; BINCOLETTO, CLAUDIA; URESHINO, RODRIGO P.; SMAILI, SORAYA S.; et al. Cannabidiol induces autophagy via ERK1/2 activation in neural cells. SCIENTIFIC REPORTS, v. 11, n. 1, MAR 8 2021. (18/06260-8, 19/02821-8, 19/14722-4, 17/10863-7, 16/20796-2)

ERUSTES, ADOLFO GARCIA; D'ELETTO, MANUELA; GUARACHE, GABRIEL CICOLIN; URESHINO, RODRIGO PORTES; BINCOLETTO, CLAUDIA; DA SILVA PEREIRA, GUSTAVO JOSE; PIACENTINI, MAURO; SMAILI, SORAYA SOUBHI. Overexpression of alpha-synuclein inhibits mitochondrial Ca2+ trafficking between the endoplasmic reticulum and mitochondria through MAMs by altering the GRP75-IP3R interaction. Journal of Neuroscience Research, v. 99, n. 11, SEP 2021. (19/02821-8, 16/05580-3, 17/10863-7, 13/20073-2, 19/14722-4, 16/20796-2)