Pan Hope, Balbirnie Melinda, Hou Ke, Sta Maria Naomi S, Sahay Shruti, Denver Paul, Lepore Stefano, Jones Mychica, Zuo Xiaohong, Zhu Chunni, Mirbaha Hilda, Shahpasand-Kroner Hedieh, Mekkittikul Marisa, Lu Jiahui, Hu Carolyn J, Cheng Xinyi, Abskharon Romany, Sawaya Michael R, Williams Christopher K, Vinters Harry V, Jacobs Russell E, Harris Neil G, Cole Gregory M, Frautschy Sally A, Eisenberg David S
Department of Chemistry and Biochemistry, Department of Biological Chemistry, UCLA-DOE Institute, Molecular Biology Institute, UCLA, Los Angeles, CA, USA.
Department of Research Physiology, Department of Neuroscience, Keck School of Medicine at USC, Los Angeles, CA, USA.
NPJ Parkinsons Dis. 2025 Apr 23;11(1):88. doi: 10.1038/s41531-025-00918-z.
Aggregation of the protein α-synuclein (α-syn) is the histopathological hallmark of neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), which are collectively known as synucleinopathies. Currently, patients with synucleinopathies are diagnosed by physical examination and medical history, often at advanced stages of disease. Because synucleinopathies are associated with α-syn aggregates, and α-syn aggregation often precedes onset of symptoms, detecting α-syn aggregates would be a valuable early diagnostic for patients with synucleinopathies. Here, we design a liganded magnetic nanoparticle (LMNP) functionalized with an α-syn-targeting peptide to be used as a magnetic resonance imaging (MRI)-based biomarker for α-syn. Our LMNPs bind to aggregates of α-syn in vitro, cross the blood-brain barrier in mice with mannitol adjuvant, and can be used as an MRI contrast agent to distinguish mice with α-synucleinopathy from age-matched, wild-type control mice in vivo. These results provide evidence for the potential of magnetic nanoparticles that target α-syn for diagnosis of synucleinopathies.
蛋白质α-突触核蛋白（α-syn）的聚集是帕金森病（PD）、路易体痴呆（DLB）和多系统萎缩（MSA）等神经退行性疾病的组织病理学标志，这些疾病统称为突触核蛋白病。目前，突触核蛋白病患者通常在疾病晚期通过体格检查和病史进行诊断。由于突触核蛋白病与α-syn聚集体相关，且α-syn聚集通常先于症状出现，因此检测α-syn聚集体对突触核蛋白病患者而言将是一种有价值的早期诊断方法。在此，我们设计了一种用α-syn靶向肽功能化的配体磁性纳米颗粒（LMNP），用作基于磁共振成像（MRI）的α-syn生物标志物。我们的LMNP在体外与α-syn聚集体结合，在甘露醇辅助下穿过小鼠血脑屏障，并可作为MRI造影剂在体内区分患有α-突触核蛋白病的小鼠和年龄匹配的野生型对照小鼠。这些结果为靶向α-syn的磁性纳米颗粒用于诊断突触核蛋白病的潜力提供了证据。
