Ribose-cysteine and levodopa abrogate Parkinsonism via the regulation of neurochemical and redox activities in alpha-synuclein transgenic Drosophila melanogaster models.

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Fly Pub Date : 2024-12-01 Epub Date: 2024-01-29 DOI:10.1080/19336934.2024.2306687
Olumayowa K Idowu, Ademola A Oremosu, Olufunke O Dosumu, Abdullahi A Mohammed
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引用次数: 0

Abstract

Parkinson's disease (PD), the most prevalent type of parkinsonism, is a progressive neurodegenerative condition marked by several non-motor and motor symptoms. PD is thought to have a complex aetiology that includes a combination of age, genetic predisposition, and environmental factors. Increased expression of α-synuclein (α-Syn) protein is central to the evolvement of neuropathology in this devastating disorder, but the potential of ribose-cysteine and levodopa in abating pathophysiologic changes in PD model is unknown. Crosses were set up between flies conditionally expressing a pathological variant of human α-Syn (UAS-α-Syn) and those expressing GAL4 in neurons (elav-GAL4) to generate offspring referred to as PD flies. Flies were randomly assigned to five groups (n = 40) from the total population of flies, with each group having five replicates. Groups of PD flies were treated with either 500 mg/kg ribose-cysteine diet, 250 mg/kg levodopa diet, or a combination of the two compounds for 21 days, whereas the control group (w1118) and the PD group were exposed to a diet without ribose-cysteine or levodopa. In addition to various biochemical and neurochemical assays, longevity, larval motility, and gravitaxis assays were carried out. Locomotive capability, lifespan, fecundity, antioxidant state, and neurotransmitter systems were all significantly (p < 0.05) compromised by overexpression of α-Syn. However, flies treated both ribose cysteine and levodopa showed an overall marked improvement in motor functions, lifespan, fecundity, antioxidant status, and neurotransmitter system functions. In conclusion, ribose-cysteine and levodopa, both singly and in combination, potentiated a therapeutic effect on alpha-synuclein transgenic Drosophila melanogaster models of Parkinsonism.

核糖-半胱氨酸和左旋多巴通过调节α-突触核蛋白转基因黑腹果蝇模型的神经化学和氧化还原活动来缓解帕金森症
帕金森病(Parkinson's disease,PD)是帕金森病中最常见的类型,是一种进行性神经退行性疾病,以多种非运动症状和运动症状为特征。帕金森病被认为病因复杂,包括年龄、遗传易感性和环境因素。α-突触核蛋白(α-Syn)蛋白表达的增加是这一毁灭性疾病神经病理学演变的核心,但核糖-半胱氨酸和左旋多巴在减轻 PD 模型病理生理变化方面的潜力尚不清楚。在有条件表达人类α-Syn病理变体(UAS-α-Syn)的苍蝇和在神经元中表达GAL4(elav-GAL4)的苍蝇之间建立杂交,产生的后代被称为PD苍蝇。苍蝇被随机分配到五个组(n = 40),每个组有五个重复。PD组苍蝇使用500毫克/千克的核糖-半胱氨酸饮食、250毫克/千克的左旋多巴饮食或两种化合物的组合进行21天的治疗,而对照组(w1118)和PD组则使用不含核糖-半胱氨酸或左旋多巴的饮食。除了各种生化和神经化学测定外,还进行了寿命、幼虫运动和重力轴向测定。结果表明,黑腹果蝇帕金森病模型的运动能力、寿命、繁殖力、抗氧化状态和神经递质系统均显著降低。
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来源期刊
Fly
Fly 生物-生化与分子生物学
CiteScore
2.90
自引率
0.00%
发文量
17
审稿时长
>12 weeks
期刊介绍: Fly is the first international peer-reviewed journal to focus on Drosophila research. Fly covers a broad range of biological sub-disciplines, ranging from developmental biology and organogenesis to sensory neurobiology, circadian rhythm and learning and memory, to sex determination, evolutionary biology and speciation. We strive to become the “to go” resource for every researcher working with Drosophila by providing a forum where the specific interests of the Drosophila community can be discussed. With the advance of molecular technologies that enable researchers to manipulate genes and their functions in many other organisms, Fly is now also publishing papers that use other insect model systems used to investigate important biological questions. Fly offers a variety of papers, including Original Research Articles, Methods and Technical Advances, Brief Communications, Reviews and Meeting Reports. In addition, Fly also features two unconventional types of contributions, Counterpoints and Extra View articles. Counterpoints are opinion pieces that critically discuss controversial papers questioning current paradigms, whether justified or not. Extra View articles, which generally are solicited by Fly editors, provide authors of important forthcoming papers published elsewhere an opportunity to expand on their original findings and discuss the broader impact of their discovery. Extra View authors are strongly encouraged to complement their published observations with additional data not included in the original paper or acquired subsequently.
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