Exploring Caenorhabditis elegans as Parkinson’s Disease Model: Neurotoxins and Genetic Implications

• Published in: Neurotoxicity research 2024-02, Vol.42 (1), p.11-11, Article 11
• Main Authors: da Silva, Larissa Pereira Dantas, da Cruz Guedes, Erika, Fernandes, Isabel Cristina Oliveira, Pedroza, Lucas Aleixo Leal, da Silva Pereira, Gustavo José, Gubert, Priscila
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases; alpha-Synuclein - genetics; Animals; Biomedical and Life Sciences; Biomedicine; Caenorhabditis elegans; Caenorhabditis elegans Proteins - genetics; Cell Biology; Dopamine; Humans; Neurobiology; Neurochemistry; Neurodegenerative Diseases; Neurology; Neurosciences; Neurotoxins; Parkinson Disease - genetics; Pharmacology/Toxicology; Review
• ISSN: 1029-8428; 1476-3524
• DOI: 10.1007/s12640-024-00686-3

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world, the first being Alzheimer’s disease. Patients with PD have a loss of dopaminergic neurons in the substantia nigra of the basal ganglia, which controls voluntary movements, causing a motor impairment as a result of dopaminergic signaling impairment. Studies have shown that mutations in several genes, such as SNCA , PARK2 , PINK1 , DJ-1 , ATP13A2 , and LRRK2 , and the exposure to neurotoxic agents can potentially increase the chances of PD development. The nematode Caenorhabditis elegans ( C. elegans ) plays an important role in studying the risk factors, such as genetic factors, aging, exposure to chemicals, disease progression, and drug treatments for PD. C. elegans has a conserved neurotransmission system during evolution; it produces dopamine, through the eight dopaminergic neurons; it can be used to study the effect of neurotoxins and also has strains that express human α-synuclein. Furthermore, the human PD-related genes, LRK-1, PINK-1, PDR-1, DJR-1.1, and CATP-6, are present and functional in this model. Therefore, this review focuses on highlighting and discussing the use of C. elegans an in vivo model in PD-related studies. Here, we identified that nematodes exposed to the neurotoxins, such as 6-OHDA, MPTP, paraquat, and rotenone, had a progressive loss of dopaminergic neurons, dopamine deficits, and decreased survival rate. Several studies have reported that expression of human LRRK2 (G2019S) caused neurodegeneration and pink-1 , pdr-1 , and djr-1.1 deletion caused several effects PD-related in C. elegans , including mitochondrial dysfunctions. Of note, the deletion of catp-6 in nematodes caused behavioral dysfunction, mitochondrial damage, and reduced survival. In addition, nematodes expressing α-synuclein had neurodegeneration and dopamine-dependent deficits. Therefore, C. elegans can be considered an accurate animal model of PD that can be used to elucidate to assess the underlying mechanisms implicated in PD to find novel therapeutic targets. Graphical Abstract Schematic representation of Parkinson’s disease models in Caenorhabditis elegans . In neurotoxin models, it has been observed that nematodes exposed to neurotoxic agents such as 6-OHDA, MPTP, paraquat, and rotenone can lead to PD impairments like the death of dopaminergic neurons, reduced dopamine levels, and decreased worm survival. In genetic models, mutations in several genes have the potential