Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Department of Neurosciences and Mental Health, Centro Hospitalar Universitário Lisboa Norte (CHULN), Lisbon, Portugal.
Biofactors. 2024 May-Jun;50(3):558-571. doi: 10.1002/biof.2030. Epub 2023 Dec 27.
Erythrocytes play a fundamental role in oxygen delivery to tissues and binding to inflammatory mediators. Evidences suggest that dysregulated erythrocyte function could contribute to the pathophysiology of several neurodegenerative diseases. We aimed to evaluate changes in morphological, biomechanical, and biophysical properties of erythrocytes from amyotrophic lateral sclerosis (ALS) patients, as new areas of study in this disease. Blood samples were collected from ALS patients, comparing with healthy volunteers. Erythrocytes were assessed using atomic force microscopy (AFM) and zeta potential analysis. The patients' motor and respiratory functions were evaluated using the revised ALS Functional Rating Scale (ALSFRS-R) and percentage of forced vital capacity (%FVC). Patient survival was also assessed. Erythrocyte surface roughness was significantly smoother in ALS patients, and this parameter was a predictor of faster decline in ALSFRS-R scores. ALS patients exhibited higher erythrocyte stiffness, as indicated by reduced AFM tip penetration depth, which predicted a faster ALSFRS-R score and respiratory subscore decay. A lower negative charge on the erythrocyte membrane was predictor of a faster ALSFRS-R and FVC decline. Additionally, a larger erythrocyte surface area was an independent predictor of lower survival. These changes in morphological and biophysical membrane properties of ALS patients' erythrocytes, lead to increased cell stiffness and morphological variations. We speculate that these changes might precipitate motoneurons dysfunction and accelerate disease progression. Further studies should explore the molecular alterations related to these observations. Our findings may contribute to dissect the complex interplay between respiratory function, tissue hypoxia, progression rate, and survival in ALS.
红细胞在向组织输送氧气和结合炎症介质方面起着至关重要的作用。有证据表明，红细胞功能失调可能导致多种神经退行性疾病的病理生理变化。我们旨在评估肌萎缩侧索硬化症（ALS）患者红细胞的形态、生物力学和生物物理特性的变化，这是该疾病研究的新领域。从 ALS 患者和健康志愿者中采集血样。使用原子力显微镜（AFM）和zeta 电位分析评估红细胞。使用修订后的肌萎缩侧索硬化功能评定量表（ALSFRS-R）和用力肺活量百分比（%FVC）评估患者的运动和呼吸功能。还评估了患者的生存情况。与健康志愿者相比，ALS 患者的红细胞表面粗糙度明显更平滑，该参数是 ALSFRS-R 评分下降更快的预测指标。ALS 患者的红细胞刚性更高，表现为 AFM 探针对红细胞的穿透深度降低，这预示着 ALSFRS-R 评分和呼吸子评分下降更快。红细胞膜上的负电荷越低，ALSFRS-R 和 FVC 下降速度越快。此外，红细胞表面积越大是生存时间较短的独立预测指标。这些 ALS 患者红细胞形态和生物物理膜特性的变化导致细胞刚性增加和形态变化。我们推测这些变化可能会导致运动神经元功能障碍，并加速疾病进展。进一步的研究应该探索与这些观察结果相关的分子改变。我们的发现可能有助于剖析 ALS 中呼吸功能、组织缺氧、进展速度和生存之间的复杂相互作用。
