Cannabidiol Protects Against 1‐Methyl‐4‐Phenylpyridinium and Manganese‐Induced Neurotoxicity via Nod‐Like Receptor Protein 3 Inflammasome Suppression
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
ABSTRACT Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurodegeneration, alpha‐synuclein (α‐Syn) accumulation, and neuroinflammation. The NOD‐Like Receptor (NLR) family pyrin domain containing 3 NLRP3 inflammasome has recently been identified as a central mediator of PD‐associated inflammatory responses. Cannabidiol (CBD), a non‐psychoactive phytocannabinoid, exhibits anti‐inflammatory and neuroprotective properties; however, its effects on NLRP3 inflammasome in PD remain insufficiently understood. This study investigated the neuroprotective effects of CBD‐rich oil against 1‐methyl‐4‐phenylpyridinium (MPP+) and manganese‐induced neurotoxicity in SH‐SY5Y cells. Cells were exposed to these substances with or without CBD co‐treatment, and cell viability, α‐Syn, dopamine, inflammatory markers [C reactive protein (CRP) and interleukin 18 (IL‐18)], and NLRP3 expressions were evaluated. MPP+ and manganese exposures significantly decreased cell viability and dopamine levels while increasing α‐Syn accumulation and inflammatory markers. Manganese induced an approximately twofold upregulation inmRNA and 1.5‐fold increase in protein expression. CBD co‐treatment preserved dopamine levels, attenuated α‐Syn accumulation, reduced IL‐18 and CRP concentrations, and attenuated NLRP3 expression. These findings demonstrate that CBD‐rich oil exerts neuroprotective effects in a PD cellular model by attenuating α‐Syn accumulation, preserving dopamine homeost
Abstract
ABSTRACT Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurodegeneration, alpha‐synuclein (α‐Syn) accumulation, and neuroinflammation. The NOD‐Like Receptor (NLR) family pyrin domain containing 3 NLRP3 inflammasome has recently been identified as a central mediator of PD‐associated inflammatory responses. Cannabidiol (CBD), a non‐psychoactive phytocannabinoid, exhibits anti‐inflammatory and neuroprotective properties; however, its effects on NLRP3 inflammasome in PD remain insufficiently understood. This study investigated the neuroprotective effects of CBD‐rich oil against 1‐methyl‐4‐phenylpyridinium (MPP+) and manganese‐induced neurotoxicity in SH‐SY5Y cells. Cells were exposed to these substances with or without CBD co‐treatment, and cell viability, α‐Syn, dopamine, inflammatory markers [C reactive protein (CRP) and interleukin 18 (IL‐18)], and NLRP3 expressions were evaluated. MPP+ and manganese exposures significantly decreased cell viability and dopamine levels while increasing α‐Syn accumulation and inflammatory markers. Manganese induced an approximately twofold upregulation inmRNA and 1.5‐fold increase in protein expression. CBD co‐treatment preserved dopamine levels, attenuated α‐Syn accumulation, reduced IL‐18 and CRP concentrations, and attenuated NLRP3 expression. These findings demonstrate that CBD‐rich oil exerts neuroprotective effects in a PD cellular model by attenuating α‐Syn accumulation, preserving dopamine homeostasis, which is associated with reduced NLRP3 expression and potential modulation of inflammasome‐related signaling, supporting further investigation of CBD as a potential therapeutic strategy for PD. CBD oil exhibits neuroprotective effects in Parkinson's disease models by inhibiting NLRP3 inflammasome activation. It preserves dopamine levels and reduces α‐synuclein accumulation, suggesting its potential as a therapeutic strategy against neuroinflammation and neurodegeneration. graphical