Krishnamurthy Karrthik, Pradhan Raj Kumar
Department of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, PA, United States.
Front Mol Neurosci. 2024 Jan 5;16:1279999. doi: 10.3389/fnmol.2023.1279999. eCollection 2023.
Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are debilitating neurodegenerative diseases with shared pathological features like transactive response DNA-binding protein of 43 kDa (TDP-43) inclusions and genetic mutations. Both diseases involve synaptic dysfunction, contributing to their clinical features. Synaptic biomarkers, representing proteins associated with synaptic function or structure, offer insights into disease mechanisms, progression, and treatment responses. These biomarkers can detect disease early, track its progression, and evaluate therapeutic efficacy. ALS is characterized by elevated neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) and blood, correlating with disease progression. TDP-43 is another key ALS biomarker, its mislocalization linked to synaptic dysfunction. In FTD, TDP-43 and tau proteins are studied as biomarkers. Synaptic biomarkers like neuronal pentraxins (NPs), including neuronal pentraxin 2 (NPTX2), and neuronal pentraxin receptor (NPTXR), offer insights into FTD pathology and cognitive decline. Advanced technologies, like machine learning (ML) and artificial intelligence (AI), aid biomarker discovery and drug development. Challenges in this research include technological limitations in detection, variability across patients, and translating findings from animal models. ML/AI can accelerate discovery by analyzing complex data and predicting disease outcomes. Synaptic biomarkers offer early disease detection, personalized treatment strategies, and insights into disease mechanisms. While challenges persist, technological advancements and interdisciplinary efforts promise to revolutionize the understanding and management of ALS and FTD. This review will explore the present comprehension of synaptic biomarkers in ALS and FTD and discuss their significance and emphasize the prospects and obstacles.
肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）是使人衰弱的神经退行性疾病，具有共同的病理特征，如43 kDa的反式激活反应DNA结合蛋白（TDP-43）包涵体和基因突变。这两种疾病都涉及突触功能障碍，这导致了它们的临床特征。突触生物标志物代表与突触功能或结构相关的蛋白质，有助于深入了解疾病机制、进展和治疗反应。这些生物标志物可以早期检测疾病、追踪其进展并评估治疗效果。ALS的特征是脑脊液（CSF）和血液中神经丝轻链（NfL）水平升高，这与疾病进展相关。TDP-43是另一个关键的ALS生物标志物，其定位错误与突触功能障碍有关。在FTD中，TDP-43和tau蛋白被作为生物标志物进行研究。突触生物标志物，如神经元五聚体蛋白（NPs），包括神经元五聚体蛋白2（NPTX2）和神经元五聚体蛋白受体（NPTXR），有助于深入了解FTD病理和认知衰退。机器学习（ML）和人工智能（AI）等先进技术有助于生物标志物的发现和药物开发。这项研究中的挑战包括检测的技术限制、患者之间的变异性以及将动物模型的研究结果转化应用。ML/AI可以通过分析复杂数据和预测疾病结果来加速发现。突触生物标志物提供早期疾病检测、个性化治疗策略以及对疾病机制的深入了解。虽然挑战依然存在，但技术进步和跨学科努力有望彻底改变对ALS和FTD的理解和管理。本综述将探讨目前对ALS和FTD中突触生物标志物的理解，并讨论它们的意义，强调前景和障碍。
