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
Subject
General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference51 articles.
1. Quality Control of the Mitochondrion;Ng;Dev. Cell,2021
2. The Role of Mitochondrial Dynamics and Mitophagy in Carcinogenesis, Metastasis and Therapy;Wang;Front. Cell Dev. Biol.,2020
3. Dabravolski, S.A., Nikiforov, N.G., Zhuravlev, A.D., Orekhov, N.A., Grechko, A.V., and Orekhov, A.N. (2022). Role of the MtDNA Mutations and Mitophagy in Inflammaging. Int. J. Mol. Sci., 23.
4. A Molecular Approach to Mitophagy and Mitochondrial Dynamics;Yoo;Mol. Cells,2018
5. Mitochondrial Dysfunction in Parkinson’s Disease: New Mechanistic Insights and Therapeutic Perspectives;Park;Curr. Neurol. Neurosci. Rep.,2018
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献