量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Patients with Parkinson’s disease (PD) show a common progressive neurodegenerative movement disorder
characterized by rigidity, tremors, postural instability, and bradykinesia due to the loss of dopaminergic neurons
in the substantia nigra, and is often accompanied by several non-motor symptoms, called parkinsonism. Several
lines of recent evidence support the hypothesis that mutations in the gene encoding phosphoglycerate kinase
(PGK) play an important role in the PD mechanism. PGK is a key enzyme in the glycolytic pathway that catalyzes
the reaction from 1,3-diphosphoglycerate to 3-phosphoglycerate. We herein established a parkinsonism model
targeting Drosophila Pgk. Dopaminergic (DA) neuron-specific Pgk knockdown lead to locomotive defects in both
young and aged adult flies and was accompanied by progressive DA neuron loss with aging. Pgk knockdown in
DA neurons decreased dopamine levels in the central nervous system (CNS) of both young and aged adult flies.
These phenotypes are similar to the defects observed in human PD patients, suggesting that the Pgk knockdown
flies established herein are a promising model for parkinsonism. Furthermore, pan-neuron-specific Pgk knockdown
induced low ATP levels and the accumulation of reactive oxygen species (ROS) in the CNS of third instar
larvae. Collectively, these results indicate that a failure in the energy production system of Pgk knockdown flies
causes locomotive defects accompanied by neuronal dysfunction and degeneration in DA neurons.
Novel Drosophila model for parkinsonism by targeting phosphoglycerate kinase
