Liang Qifei, Zhao Guangrong
Tongji University School of Medicine, Shanghai, China.
Nanjing Drum Tower Hospital, Nanjing, China.
J Clin Lab Anal. 2024 Dec;38(24):e25129. doi: 10.1002/jcla.25129. Epub 2024 Nov 26.
Parkinson's disease (PD) is a common neurodegenerative disease. Glutamate(Glu) excitotoxicity is one of the main pathogenesis of PD. Glutaminase (Gls) is an enzyme primarily responsible for catalyzing the hydrolysis and deamidation of glutamine (Gln) to produce Glu and ammonia. Inhibiting the function of Gls may have a beneficial effect on the treatment of PD by reducing the production of Glu. The homologous gene of Gls in C. elegans is glna.
To explore the effects of glna loss on physiological and pathological phenotype of PD C. elegans, and to provide new ideas and references for the research and treatment of PD.
MATERIALS & METHODS: We used PD C. elegans UA44 and QIN27 to detect development and lifespan, behavior, degeneration of dopaminergic neurons, lipid levels, ROS levels, expression levels of common amino acids.
Glna loss had no significant impact on the development and lifespan of PD C. elegans. Glna loss saved part of the decline of motor function, including the head thrash frequency and the body bend frequency, and the difference was significant. There was a trend of improvement in some motor behaviors, such as the ethanol avoidance experiment, while no improvement was observed in other experiments. Glna loss slowed down the degeneration of dopaminergic neurons. Glna loss increased the lipid levels and ROS levels in C. elegans. Glna loss decreased Glu content and increased Gln content in C. elegans.
The effect of glna loss on PD C. elegans may be the result of multiple factors, such as the tissue types of α-syn expression in C. elegans, the PD C. elegans model used, the adverse effects of glna loss on other systems, and the changes in ROS levels in C. elegans. The specific mechanisms causing these phenomena are still unclear and need to be further explored.
Glna loss has a certain protective effect on dopaminergic neurons in PD C. elegans, while the improvement effect on movement and behavior is limited.
帕金森病（PD）是一种常见的神经退行性疾病。谷氨酸（Glu）兴奋性毒性是PD的主要发病机制之一。谷氨酰胺酶（Gls）是一种主要负责催化谷氨酰胺（Gln）水解和脱酰胺作用以产生Glu和氨的酶。抑制Gls的功能可能通过减少Glu的产生对PD的治疗产生有益作用。秀丽隐杆线虫中Gls的同源基因是glna。
探讨glna缺失对PD秀丽隐杆线虫生理和病理表型的影响，为PD的研究和治疗提供新思路和参考。
我们使用PD秀丽隐杆线虫UA44和QIN27检测发育和寿命、行为、多巴胺能神经元退变、脂质水平、活性氧水平、常见氨基酸表达水平。
glna缺失对PD秀丽隐杆线虫的发育和寿命没有显著影响。glna缺失挽救了部分运动功能的下降，包括头部摆动频率和身体弯曲频率，差异显著。在一些运动行为如乙醇回避实验中有改善趋势，而在其他实验中未观察到改善。glna缺失减缓了多巴胺能神经元的退变。glna缺失增加了秀丽隐杆线虫的脂质水平和活性氧水平。glna缺失降低了秀丽隐杆线虫中Glu含量并增加了Gln含量。
glna缺失对PD秀丽隐杆线虫的影响可能是多种因素的结果，如秀丽隐杆线虫中α-突触核蛋白表达的组织类型、所使用的PD秀丽隐杆线虫模型、glna缺失对其他系统的不利影响以及秀丽隐杆线虫中活性氧水平的变化。导致这些现象的具体机制仍不清楚，需要进一步探索。
glna缺失对PD秀丽隐杆线虫中的多巴胺能神经元有一定的保护作用，而对运动和行为的改善作用有限。
