Brun-Cosme-Bruny M, Gerfault L, Mourier V, Torres N, Bleuet P
Univ. Grenoble Alpes, CEA, Leti, Clinatec, 38000, Grenoble, France.
Univ. Grenoble Alpes, CEA, Leti, 38000, Grenoble, France.
Protein J. 2025 Feb;44(1):62-67. doi: 10.1007/s10930-024-10241-w. Epub 2024 Dec 4.
Over the past decades, the incidence of Parkinson's disease (PD) cases has doubled in industrialized countries. While patients over 70 years old still represent more than half of the cases, the disease is increasingly affecting younger individuals. Environmental factors have been implicated, such as the effects of certain pesticides or chemicals on neurons, such as rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Researchers have also demonstrated the influence of genetic mutations in younger patients. A-synuclein is a protein encoded by the SNCA gene, known to undergo various mutations in hereditary cases of PD. These mutations alter the composition and spatial arrangements of α-synuclein. The proteins, originally of linear shape, aggregate during the progression of PD, forming fibrillary structures that propagate through brain tissues. Among the physical therapies investigated for treating α-synuclein aggregation, ultrasonic waves, capable of altering protein and cell behaviors, have recently been used to disrupt α-synuclein fibrils within tissues in cellular and animal models, with the hope of developing treatments based on ultrasound properties. However, detecting fibrils typically requires invasive and non-biocompatible chemical compounds or cumbersome machinery. In this study, our acoustic experimental setup allowed us to investigate the response of α-synuclein to ultrasound perturbations. By capturing the transmitted wave across proteins over a frequency range 10 kHz to 10 MHz, no ultrasound signature indicating the presence of proteins was observed.Significance Statement: The results report there is no ultrasound signature of the presence of α-synuclein fibrils, from 10 kHz to 10 MHz.
在过去几十年中，帕金森病（PD）病例的发病率在工业化国家已翻了一番。虽然70岁以上的患者仍占病例的一半以上，但该疾病正越来越多地影响年轻个体。环境因素已被牵连其中，例如某些农药或化学物质对神经元的影响，如鱼藤酮或1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）。研究人员还证明了基因突变在年轻患者中的影响。α-突触核蛋白是由SNCA基因编码的一种蛋白质，已知在PD的遗传病例中会发生各种突变。这些突变改变了α-突触核蛋白的组成和空间排列。这些原本呈线性的蛋白质在PD进展过程中聚集，形成通过脑组织传播的纤维状结构。在研究用于治疗α-突触核蛋白聚集的物理疗法中，能够改变蛋白质和细胞行为的超声波最近已被用于破坏细胞和动物模型组织内的α-突触核蛋白原纤维，希望基于超声特性开发治疗方法。然而，检测原纤维通常需要侵入性且非生物相容性的化合物或笨重的仪器。在本研究中，我们的声学实验装置使我们能够研究α-突触核蛋白对超声扰动的反应。通过在10kHz至10MHz频率范围内捕获穿过蛋白质的透射波，未观察到表明蛋白质存在的超声信号。意义声明：结果报告在10kHz至10MHz范围内不存在α-突触核蛋白原纤维的超声信号。
