Parkinsonism & related disorders · 2026
Molecular analysis of mitochondrial complex I in the levodopa short duration response in Parkinson's disease.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Bispo Ana Gabrielle, Souza Felipe Gouvêa de, Epifane-de-Assunção Matheus, Sena-Dos-Santos Camille, Barra-Matos Gustavo, Moura Dafne Dalledone, Eufraseo Gracivane Lopes, Silva Caio Santos, Santana-de-Araújo Gilderlanio, Ribeiro-Dos-Santos Ândrea, Santos-Lobato Bruno Lopes, Cavalcante Giovanna C
Аннотация
INTRODUCTION: Significant advances have been made in elucidating the pathophysiological mechanisms of Parkinson's disease (PD). Levodopa remains the main therapeutic option - although it presents heterogeneous clinical benefits among patients. Mutations related to levodopa metabolic pathways have been investigated, but not for mtDNA. Since levodopa metabolism is highly dependent on ionic gradients, endocytosis, and vesicular transport - all ATP-dependent processes - the normal function of OXPHOS is essential not only for adequate levodopa metabolism but also for its therapeutic efficacy. This study aimed to analyze levodopa short duration responsiveness profiles considering the mitochondrial genomic component in Brazilian admixed populations.
METHODS: A total of 49 patients with PD underwent a levodopa challenge test (LCT), followed by whole mitochondrial genome sequencing, pathogenicity prediction of identified variants, and in silico structural analyses.
RESULTS: Variants most frequently affected ND4, ND5, and ND6 subunits in both groups (responsive and non-responsive). Among them, the responsive group presented variants in MT-ND4 (m.12018C > G - T420S) and ND5 (m.13130C > A - P265H) as those with the most significant structural impact, suggesting a loss of the native conformation and alterations in protein efficiency. Additionally, five unique variants were detected only among non-responsive patients, two of which were absent from the dbSNP and ClinVar databases, which indicates the possibility that they are novel variants and potentially population-specific.
CONCLUSION: We provide molecular evidence suggesting that variants in mitochondrial ND4, ND5, and ND6 subunits, in addition to mitochondrial ancestry, may contribute to distinct levodopa short duration response in PD patients.
METHODS: A total of 49 patients with PD underwent a levodopa challenge test (LCT), followed by whole mitochondrial genome sequencing, pathogenicity prediction of identified variants, and in silico structural analyses.
RESULTS: Variants most frequently affected ND4, ND5, and ND6 subunits in both groups (responsive and non-responsive). Among them, the responsive group presented variants in MT-ND4 (m.12018C > G - T420S) and ND5 (m.13130C > A - P265H) as those with the most significant structural impact, suggesting a loss of the native conformation and alterations in protein efficiency. Additionally, five unique variants were detected only among non-responsive patients, two of which were absent from the dbSNP and ClinVar databases, which indicates the possibility that they are novel variants and potentially population-specific.
CONCLUSION: We provide molecular evidence suggesting that variants in mitochondrial ND4, ND5, and ND6 subunits, in addition to mitochondrial ancestry, may contribute to distinct levodopa short duration response in PD patients.