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Rotenone-Induced Model of Parkinson’s Disease: Beyond Mitochondrial Complex I Inhibition

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Abstract

Parkinson’s disease (PD) is usually diagnosed through motor symptoms that make the patient incapable of carrying out daily activities; however, numerous non-motor symptoms include olfactory disturbances, constipation, depression, excessive daytime sleepiness, and rapid eye movement at sleep; they begin years before motor symptoms. Therefore, several experimental models have been studied to reproduce several PD functional and neurochemical characteristics; however, no model mimics all the PD motor and non-motor symptoms to date, which becomes a limitation for PD study. It has become increasingly relevant to find ways to study the disease from its slowly progressive nature. The experimental models most frequently used to reproduce PD are based on administering toxic chemical compounds, which aim to imitate dopamine deficiency. The most used toxic compounds to model PD have been 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), which inhibit the complex I of the electron transport chain but have some limitations. Another toxic compound that has drawn attention recently is rotenone, the classical inhibitor of mitochondrial complex I. Rotenone triggers the progressive death of dopaminergic neurons and α-synuclein inclusions formation in rats; also, rotenone induces microtubule destabilization. This review presents information about the experimental model of PD induced by rotenone, emphasizing its molecular characteristics beyond the inhibition of mitochondrial complex I.

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Acknowledgements

Ibarra-Gutiérrez M. T. is a PhD student from Programa de Doctorado en Ciencias Biomédicas at the Universidad Nacional Autónoma de México (UNAM) and received the fellowship 414232 from the Consejo Nacional de Ciencia y Tecnología, México.

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  1. Laboratorio de Neurobiología Molecular y Celular, Instituto Nacional de Neurología y Neurocirugía, Av. Insurgentes Sur No. 3877 Col. La Fama, Tlalpan, C.P. 14269, Ciudad de Mexico, Mexico

    María Teresa Ibarra-Gutiérrez, Norma Serrano-García & Marisol Orozco-Ibarra

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  1. María Teresa Ibarra-Gutiérrez
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  2. Norma Serrano-García
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  3. Marisol Orozco-Ibarra
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All authors contributed to the study conception. Maria Teresa Ibarra-Gutiérrez wrote the first draft of the manuscript under the supervision of Marisol Orozco-Ibarra; all authors performed the revision considering the reviewer’s suggestion. Finally, all authors read and approved the final manuscript.

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Correspondence to Marisol Orozco-Ibarra.

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Ibarra-Gutiérrez, M.T., Serrano-García, N. & Orozco-Ibarra, M. Rotenone-Induced Model of Parkinson’s Disease: Beyond Mitochondrial Complex I Inhibition. Mol Neurobiol 60, 1929–1948 (2023). https://doi.org/10.1007/s12035-022-03193-8

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