Prevail Therapeutics, a Wholly Owned Subsidiary of Eli Lilly and Company, New York, NY 10016, USA.
Int J Mol Sci. 2023 Dec 21;25(1):131. doi: 10.3390/ijms25010131.
Biomarkers are molecules that can be used to observe changes in an individual's biochemical or medical status and provide information to aid diagnosis or treatment decisions. Dysregulation in lipid metabolism in the brain is a major risk factor for many neurodegenerative disorders, including frontotemporal dementia, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Thus, there is a growing interest in using lipids as biomarkers in neurodegenerative diseases, with the anionic phospholipid bis(monoacylglycerol)phosphate and (glyco-)sphingolipids being the most promising lipid classes thus far. In this review, we provide a general overview of lipid biology, provide examples of abnormal lysosomal lipid metabolism in neurodegenerative diseases, and discuss how these insights might offer novel and promising opportunities in biomarker development and therapeutic discovery. Finally, we discuss the challenges and opportunities of lipid biomarkers and biomarker panels in diagnosis, prognosis, and/or treatment response in the clinic.
生物标志物是可用于观察个体生化或医学状态变化并提供信息以辅助诊断或治疗决策的分子。大脑脂质代谢失调是许多神经退行性疾病的主要风险因素，包括额颞叶痴呆、阿尔茨海默病、帕金森病和肌萎缩侧索硬化症。因此，人们越来越有兴趣将脂质作为神经退行性疾病的生物标志物，阴离子磷脂双（单酰基甘油）磷酸酯和（糖）神经鞘脂是迄今为止最有前途的脂质类别。在这篇综述中，我们提供了脂质生物学的概述，提供了神经退行性疾病中溶酶体脂质代谢异常的例子，并讨论了这些见解如何在生物标志物开发和治疗发现中提供新的、有前途的机会。最后，我们讨论了脂质生物标志物和生物标志物在临床诊断、预后和/或治疗反应中的挑战和机遇。
