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

Autor: da Silva LPD; Keizo Asami Institute, iLIKA, Universidade Federal de Pernambuco, Moraes Rego Avenue, 1235, Recife, Pernambuco, 50670-901, Brazil., da Cruz Guedes E; Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil., Fernandes ICO; Keizo Asami Institute, iLIKA, Universidade Federal de Pernambuco, Moraes Rego Avenue, 1235, Recife, Pernambuco, 50670-901, Brazil.; Postgraduate Program in Biological Science, Universidade Federal de Pernambuco, Pernambuco, Recife, Brazil., Pedroza LAL; Keizo Asami Institute, iLIKA, Universidade Federal de Pernambuco, Moraes Rego Avenue, 1235, Recife, Pernambuco, 50670-901, Brazil., da Silva Pereira GJ; Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil., Gubert P; Keizo Asami Institute, iLIKA, Universidade Federal de Pernambuco, Moraes Rego Avenue, 1235, Recife, Pernambuco, 50670-901, Brazil. priscila.gubert@ufpe.br.; Postgraduate Program in Biological Science, Universidade Federal de Pernambuco, Pernambuco, Recife, Brazil. priscila.gubert@ufpe.br.; Postgraduate Program in Pure and Applied Chemistry, Universidade Federal do Oeste da Bahia, Bahia, Brazil. priscila.gubert@ufpe.br.
Jazyk: angličtina
Zdroj: Neurotoxicity research [Neurotox Res] 2024 Feb 06; Vol. 42 (1), pp. 11. Date of Electronic Publication: 2024 Feb 06.
DOI: 10.1007/s12640-024-00686-3
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: