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蛋白质组学在进行性核上性麻痹深度分子研究中的潜力。

The potential of proteomics for in-depth molecular investigations of progressive supranuclear palsy.

作者信息

Romero-Murillo Silvia, Lee Seojin, Fernández-Irigoyen Joaquín, Martinez-Valbuena Ivan, Santamaría Enrique

机构信息

Clinical Neuroproteomics Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.

出版信息

Expert Rev Proteomics. 2025 Jun;22(6):225-235. doi: 10.1080/14789450.2025.2519466. Epub 2025 Jun 17.

Abstract

INTRODUCTION

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder. The lack of comprehension about the pathogenesis of the disease, its heterogeneity, and the complex clinical evaluation in early stages, limit the development of effective treatments for PSP patients and highlight the need of further research on the field.

AREAS COVERED

In this work, we review the current knowledge of the physio- and neuropathology of PSP, its clinical features, diagnosis markers, and treatment options. We also compare the proteomic-based studies done to date in brain tissues as well as in cerebrospinal fluid and other non-cerebral samples, briefly describing the proteomic approach used and the biological findings obtained in each study.

EXPERT OPINION

PSP is a complex neurodegenerative disorder marked by tau aggregation, glial dysfunction, and neuroinflammation. Although advances in neuroimaging and biofluid biomarkers have improved PSP diagnostic accuracy, no disease-modifying therapies are currently available. Promising avenues such as tau PET tracers, seed amplification assays, and advanced proteomic-based approaches are enhancing our ability to detect disease-specific tau pathology and hold the potential to provide novel biomarkers for earlier and more precise clinical diagnosis and treatment development that could transform the landscape of PSP.

摘要

引言

进行性核上性麻痹(PSP)是一种罕见的神经退行性疾病。对该疾病发病机制、其异质性以及早期复杂临床评估的认识不足,限制了针对PSP患者的有效治疗方法的开发,并凸显了该领域进一步研究的必要性。

涵盖领域

在这项工作中,我们回顾了PSP的生理和神经病理学、其临床特征、诊断标志物及治疗选择的当前知识。我们还比较了迄今为止在脑组织、脑脊液及其他非脑样本中进行的基于蛋白质组学的研究,简要描述了每项研究中使用的蛋白质组学方法及获得的生物学发现。

专家观点

PSP是一种复杂的神经退行性疾病,其特征为tau蛋白聚集、胶质细胞功能障碍和神经炎症。尽管神经影像学和生物流体生物标志物方面的进展提高了PSP的诊断准确性,但目前尚无改善病情的疗法。诸如tau正电子发射断层扫描示踪剂、种子扩增检测和先进的基于蛋白质组学的方法等有前景的途径,正在增强我们检测疾病特异性tau病理学的能力,并有可能提供新的生物标志物,用于更早、更精确的临床诊断和治疗开发,这可能会改变PSP的局面。

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