The diagnosis of neurodegenerative disorders is often challenging due to the lack of diagnostic tools, comorbidities and shared pathological manifestations. Synaptic dysfunction is an early pathological event in many neurodegenerative disorders, but the underpinning mechanisms are still poorly characterised. Reliable quantification of synaptic damage is crucial to understand the pathophysiology of neurodegeneration, to track disease status and to obtain prognostic information. Neuronal pentraxins (NPTXs) are extracellular scaffolding proteins emerging as potential biomarkers of synaptic dysfunction in neurodegeneration. They are a family of proteins involved in homeostatic synaptic plasticity by recruiting post-synaptic receptors into synapses. Recent research investigates the dynamic changes of NPTXs in the cerebrospinal fluid (CSF) as an expression of synaptic damage, possibly related to cognitive impairment. In this review, we summarise the available data on NPTXs structure and expression patterns as well as on their contribution in synaptic function and plasticity and other less well-characterised roles. Moreover, we propose a mechanism for their involvement in synaptic damage and neurodegeneration and assess their potential as CSF biomarkers for neurodegenerative diseases.

由于缺乏诊断工具、合并症和共同的病理表现，神经退行性疾病的诊断通常具有挑战性。突触功能障碍是许多神经退行性疾病的早期病理事件，但其基础机制仍知之甚少。突触损伤的可靠量化对于了解神经退行性变的病理生理学、跟踪疾病状态和获得预后信息至关重要。神经元五聚蛋白 (NPTX) 是细胞外支架蛋白，是神经退行性疾病中突触功能障碍的潜在生物标志物。它们是通过将突触后受体募集到突触中而参与稳态突触可塑性的蛋白质家族。最近的研究调查了脑脊液 (CSF) 中 NPTX 的动态变化，作为突触损伤的表达，可能与认知障碍有关。在这篇综述中，我们总结了有关 NPTX 结构和表达模式以及它们对突触功能和可塑性以及其他不太明确的作用的贡献的可用数据。此外，我们提出了它们参与突触损伤和神经退行性变的机制，并评估了它们作为神经退行性疾病脑脊液生物标志物的潜力。