MTA-SZTE, Neuroscience Research Group, Semmelweis u. 6, H-6725 Szeged, Hungary.
Department of Neurology, Interdisciplinary Excellence Centre, Faculty of Medicine, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
Int J Mol Sci. 2020 Dec 8;21(24):9338. doi: 10.3390/ijms21249338.
Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to the abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes, which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. This review article discusses current knowledge of KP alterations observed in the central nervous system as well as the periphery, its involvement in pathogenesis and disease progression, and emerging evidence of roles of microbiota in the gut-brain axis, searching for practical peripheral biomarkers which ensure personalized treatment plans for neurodegenerative diseases.
神经退行性疾病是多因素的,由一系列病因复合体引发,发展成特定的临床症状。发病机制和病程因患者而异。因此,治疗方法也应因人而异。外周生物标志物对于为患有神经退行性疾病(如阿尔茨海默病、帕金森病和多发性硬化症等)的患者制定个性化治疗方案至关重要。然而,生物标志物在临床实践中的应用仍未得到充分重视,与药物研发中可用的丰富数据相比,生物标志物研究中用于临床应用的数据仍然缺乏说服力。犬尿氨酸(KYN)及其犬尿氨酸途径(KP)酶也是如此,它们与多种疾病有关,包括癌症、自身免疫性疾病、炎症性疾病、神经退行性疾病和精神疾病。本文综述了中枢神经系统和外周神经系统中观察到的 KP 改变的最新知识,及其在发病机制和疾病进展中的作用,以及微生物群在肠脑轴中的作用的新证据,寻找实用的外周生物标志物,以确保神经退行性疾病的个性化治疗方案。