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01.02.2024 | Review

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

verfasst von: Larissa Pereira Dantas da Silva, Erika da Cruz Guedes, Isabel Cristina Oliveira Fernandes, Lucas Aleixo Leal Pedroza, Gustavo José da Silva Pereira, Priscila Gubert

Erschienen in: Neurotoxicity Research | Ausgabe 1/2024

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Abstract

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 to increase the probability of PD development. The expression of human LRRK2 (G2019S) can induce neurodegeneration in worms, while the deletion of genes like pink-1, pdr-1, djr-1.1, and catp-6 is associated with behavioral dysfunction, mitochondrial damage, and decreased survival.

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Titel: Exploring Caenorhabditis elegans as Parkinson’s Disease Model: Neurotoxins and Genetic Implications
verfasst von: Larissa Pereira Dantas da Silva
Erika da Cruz Guedes
Isabel Cristina Oliveira Fernandes
Lucas Aleixo Leal Pedroza
Gustavo José da Silva Pereira
Priscila Gubert
Publikationsdatum: 01.02.2024
Verlag: Springer US
Erschienen in: Neurotoxicity Research / Ausgabe 1/2024
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-024-00686-3

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