Metabolic alterations in a Drosophila model of Parkinson’s disease based on DJ-1 deficiency
Metabolic alterations in a Drosophila model of Parkinson’s disease based on DJ-1 deficiency
ABSTRACT Parkinson’s disease (PD) is the second most common neurodegenerative disorder whose physiopathology is still unclear. Besides, it is urgent to discover new biomarkers and therapeutic targets to facilitate its diagnosis and treatment. Previous studies performed in PD models and samples from PD patients already demonstrated that metabolic alterations were associated with this disease. In this context, the aim of this study is to give a better understanding of metabolic disturbances underlying PD pathogenesis. To achieve this goal, we used a Drosophila PD model based on inactivation of the DJ-1β gene (ortholog of human DJ-1). Metabolomic analyses were performed in 1-day-old and 15-day-old DJ-1β mutants and control flies using 1H nuclear magnetic resonance spectroscopy, combined with expression and enzymatic activity assays of proteins implicated in altered pathways. Our results showed that PD model flies exhibit protein metabolism alterations, a shift from tricarboxylic acid cycle to glycolytic pathway to obtain ATP, together with an increase in the expression of some urea cycle enzymes. Thus, these metabolic changes could be contributing to PD pathogenesis and might constitute possible therapeutic targets and/or biomarkers for this disease.
Sanz Francisco Jos¨|、Hern¨￠ndez-Oliver Carolina、Palomino-Sch?tzlein Martina、Solana-Manrique Cristina、Paricio Nuria、Torregrosa Isabel、Pineda Antonio
Departamento de Gen¨|tica, Facultad CC Biol¨?gicas, Universidad de Valencia||Instituto Universitario de Biotecnolog¨aa y Biomedicina (BIOTECMED), Universidad de ValenciaStructural Biochemistry Laboratory, Centro de Investigaci¨?n Pr¨ancipe Felipe||Joint Research Unit in Clinical Metabolomics CIPF/IIS La Fe, Drug Discovery UnitStructural Biochemistry Laboratory, Centro de Investigaci¨?n Pr¨ancipe Felipe||Joint Research Unit in Clinical Metabolomics CIPF/IIS La Fe, Drug Discovery UnitDepartamento de Gen¨|tica, Facultad CC Biol¨?gicas, Universidad de Valencia||Instituto Universitario de Biotecnolog¨aa y Biomedicina (BIOTECMED), Universidad de ValenciaDepartamento de Gen¨|tica, Facultad CC Biol¨?gicas, Universidad de Valencia||Instituto Universitario de Biotecnolog¨aa y Biomedicina (BIOTECMED), Universidad de ValenciaDepartamento de Gen¨|tica, Facultad CC Biol¨?gicas, Universidad de Valencia||Instituto Universitario de Biotecnolog¨aa y Biomedicina (BIOTECMED), Universidad de ValenciaStructural Biochemistry Laboratory, Centro de Investigaci¨?n Pr¨ancipe Felipe||Joint Research Unit in Clinical Metabolomics CIPF/IIS La Fe, Drug Discovery Unit
神经病学、精神病学生物化学基础医学
DrosophilaDJ-1Parkinson’s diseasemetabolomicsNMR spectroscopy
Sanz Francisco Jos¨|,Hern¨￠ndez-Oliver Carolina,Palomino-Sch?tzlein Martina,Solana-Manrique Cristina,Paricio Nuria,Torregrosa Isabel,Pineda Antonio.Metabolic alterations in a Drosophila model of Parkinson’s disease based on DJ-1 deficiency[EB/OL].(2025-03-28)[2025-05-05].https://www.biorxiv.org/content/10.1101/2021.12.15.472768.点此复制
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