Mathew Blessy Aksa, Katta Madhumitha, Ludhiadch Abhilash, Singh Paramdeep, Munshi Anjana
Complex Disease Genomics and Precision Medicine Laboratory, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, India, 151401.
Department of Radiology, All India Institute of Medical Sciences, Bathinda, Punjab, India, 151001.
Mol Neurobiol. 2023 Feb;60(2):655-671. doi: 10.1007/s12035-022-03078-w. Epub 2022 Nov 8.
tRFs are small tRNA derived fragments that are emerging as novel therapeutic targets and regulatory molecules in the pathophysiology of various neurological disorders. These are derived from precursor or mature tRNA, forming different subtypes that have been reported to be involved in neurological disorders like stroke, Alzheimer's, epilepsy, Parkinson's, MELAS, autism, and Huntington's disorder. tRFs were earlier believed to be random degradation debris of tRNAs. The significant variation in the expression level of tRFs in disease conditions indicates their salient role as key players in regulation of these disorders. Various animal studies are being carried out to decipher their exact role; however, more inputs are required to transform this research knowledge into clinical application. Future investigations also call for high-throughput technologies that could help to bring out the other hidden aspects of these entities. However, studies on tRFs require further research efforts to overcome the challenges posed in quantifying tRFs, their interactions with other molecules, and the exact mechanism of function. In this review, we are abridging the current understanding of tRFs, including their biogenesis, function, relevance in clinical therapies, and potential as diagnostic and prognostic biomarkers of these neurological disorders.
tRFs是小的tRNA衍生片段,正逐渐成为各种神经疾病病理生理学中的新型治疗靶点和调节分子。它们来源于前体或成熟tRNA,形成不同的亚型,据报道这些亚型与中风、阿尔茨海默病、癫痫、帕金森病、线粒体脑肌病伴乳酸血症和卒中样发作(MELAS)、自闭症以及亨廷顿病等神经疾病有关。tRFs曾被认为是tRNA的随机降解碎片。疾病状态下tRFs表达水平的显著差异表明它们在这些疾病的调节中作为关键参与者发挥着重要作用。正在进行各种动物研究以解读它们的确切作用;然而,需要更多的投入才能将这些研究知识转化为临床应用。未来的研究还需要高通量技术,以帮助揭示这些实体的其他隐藏方面。然而,关于tRFs的研究需要进一步的研究努力,以克服在量化tRFs、它们与其他分子的相互作用以及确切的功能机制方面所面临的挑战。在这篇综述中,我们总结了目前对tRFs的认识,包括它们的生物合成、功能、在临床治疗中的相关性以及作为这些神经疾病诊断和预后生物标志物的潜力。