Investigation of PRKN Mutations in Levodopa-Induced Dyskinesia in Parkinson’s Disease Treatment

Author:

Bispo Ana Gabrielle1,Silva Caio S.1ORCID,Sena-dos-Santos Camille1,Dalledone Moura Dafne2,Koshimoto Brenda Hanae Bentes2,Santos-Lobato Bruno Lopes2ORCID,Ribeiro-dos-Santos Ândrea1ORCID,Cavalcante Giovanna C.1ORCID

Affiliation:

1. Laboratory of Human and Medical Genetics, Federal University of Pará, Belém 66075-110, Brazil

2. Laboratory of Experimental Neuropathology, Federal University of Pará, Belém 66075-110, Brazil

Abstract

Mitophagy is an important process that participates in mitochondrial quality control. Dysfunctions in this process can be caused by mutations in genes like PRKN and are associated with the development and progression of Parkinson’s Disease (PD). The most used drug in the treatment of PD is levodopa (LD), but it can cause adverse effects, such as dyskinesia. Currently, few studies are searching for biomarkers for an effective use of lLD for this disease, especially regarding mitophagy genetics. Thus, this work investigates the association of 14 variants of the PRKN gene with LD in the treatment of PD. We recruited 70 patients with PD undergoing treatment with LD (39 without dyskinesia and 31 with dyskinesia). Genotyping was based on Sanger sequencing. Our results reinforce that age at onset of symptoms, duration of PD, and treatment and dosage of LD can influence the occurrence of dyskinesia but not the investigated PRKN variants. The perspective presented here of variants of mitophagy-related genes in the context of treatment with LD is still underexplored, although an association has been indicated in previous studies. We suggest that other variants in PRKN or in other mitophagy genes may participate in the development of levodopa-induced dyskinesia in PD treatment.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Pró-Reitoria de Pesquisa e Pós-Graduação da Universidade Federal do Pará

Rede de Pesquisa em Genômica Populacional Humana

CNPq/MCTI/FNDCT

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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