Cannabidiol-mediated autophagy in a Caenorhabditis elegans Parkinson's disease model

• Grant number: 23/03731-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2023
• End date: June 30, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Claudia Bincoletto Trindade
• Grantee: Rodrigo Issamu Kano
• Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Ageing is the primary risk factor for most neurodegenerative diseases as Parkinson disease (PD). Several individuals affected by this disease receive palliative treatment that helps to control clinical manifestation, however, without inhibiting disease progression. Cannabidiol (CBD) has been studied on PD research, due to its effect on the central nervous system and for showing neuroprotective effect, however its mechanism is not well understood. Several evidences lead to a role for CBD in autophagy activation. Autophagy has been shown to be an important process in the context of neurodegenerative diseases, either by reducing or excessively increasing their autophagic activity. Is known that the deficiency leads to aberrant aggregation of ubiquitinated proteins within inclusion bodies, an important characteristic of the neurodegenerative processes, as Lewis body on the Parkinson's diseases, formed mostly of ±-synuclein protein. In this way, the objective of this project will be to study the effect of CBD in vivo models for Parkinson's disease, evaluating the dopaminergic neurodegeneration, ±-synuclein accumulation and the autophagy activation in this context. Transgenic C. elegans models will be used for the expression of ±-synuclein with constitutive fluorescence labeling for dopaminergic neurons and muscle. Different strains will be treated with CBD, followed by morphological analysis of dopaminergic neurons and ±-synuclein accumulation. Fluorescence microscopy techniques will be used to evaluate the neuroprotective effects of CBD, as well as to evaluate the autophagy induction. Thereby, this study may contribute to a better understanding of the potential cannabinoid therapeutic targets and their possible neuroprotective effects.