Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Department of Biochemistry, Laboratório de Imunopatologia Keizo Asami, LIKA, Federal University of Pernambuco, Recife 50670901, Brazil.
Biomolecules. 2022 Sep 29;12(10):1396. doi: 10.3390/biom12101396.
() is a nematode present worldwide. The worm shows homology to mammalian systems and expresses approximately 40% of human disease-related genes. Since Dr. Sydney Brenner first proposed as an advantageous experimental worm-model system for genetic approaches, increasing numbers of studies using as a tool to investigate topics in several fields of biochemistry, neuroscience, pharmacology, and toxicology have been performed. In this regard, has been used to characterize the molecular mechanisms and affected pathways caused by metals that lead to neurotoxicity, as well as the pathophysiological interrelationship between metal exposure and ongoing neurodegenerative disorders. Several toxic metals, such as lead, cadmium, and mercury, are recognized as important environmental contaminants, and their exposure is associated with toxic effects on the human body. Essential elements that are required to maintain cellular homeostasis and normal physiological functions may also be toxic when accumulated at higher concentrations. For instance, manganese (Mn) is a trace essential element that participates in numerous biological processes, such as enzymatic activities, energy metabolism, and maintenance of cell functions. However, Mn overexposure is associated with behavioral changes in , which are consistent with the dopaminergic system being the primary target of Mn neurotoxicity. has been shown to be an important tool that allows for studies on neuron morphology using fluorescent transgenic worms. Moreover, behavioral tests may be conducted using worms, and neurotransmitter determination and related gene expression are likely to change after Mn exposure. Likewise, mutant worms may be used to study molecular mechanisms in Mn toxicity, as well as the expression of proteins responsible for the biosynthesis, transport, storage, and uptake of dopamine. Furthermore, this review highlights some advantages and limitations of using the experimental model of and provides guidance for potential future applications of this model in studies directed toward assessing for Mn neurotoxicity and related mechanisms.
秀丽隐杆线虫是一种广泛存在于世界各地的线虫。该虫与哺乳动物系统具有同源性,表达约 40%的人类疾病相关基因。自从悉尼·布伦纳博士首次提出将秀丽隐杆线虫作为遗传方法的有利实验性线虫模型系统以来,越来越多的研究使用秀丽隐杆线虫作为工具来研究生物化学、神经科学、药理学和毒理学等多个领域的课题。在这方面,秀丽隐杆线虫已被用于表征由导致神经毒性的金属引起的分子机制和受影响的途径,以及金属暴露与正在进行的神经退行性疾病之间的病理生理相互关系。几种有毒金属,如铅、镉和汞,被认为是重要的环境污染物,它们的暴露与对人体的毒性作用有关。维持细胞内稳态和正常生理功能所需的必需元素,在浓度较高时也可能有毒。例如,锰 (Mn) 是一种痕量必需元素,参与许多生物过程,如酶活性、能量代谢和细胞功能的维持。然而,Mn 过度暴露与 中的行为变化有关,这与 Mn 神经毒性的主要靶标是多巴胺能系统一致。秀丽隐杆线虫已被证明是一种重要的工具,可用于使用荧光转基因线虫研究神经元形态。此外,可以使用线虫进行行为测试,并且在 Mn 暴露后可能会改变神经递质的测定和相关基因的表达。同样,可以使用突变体线虫来研究 Mn 毒性中的分子机制,以及负责多巴胺生物合成、运输、储存和摄取的蛋白质的表达。此外,本文还强调了使用秀丽隐杆线虫实验模型的一些优点和局限性,并为该模型在评估 Mn 神经毒性和相关机制的潜在未来应用中提供了指导。