Apostolo Daria, Ferreira Luciana L, D'Onghia Davide, Vincenzi Federica, Vercellino Nicole, Perazzi Mattia, Pirisi Mario, Cantello Roberto, Minisini Rosalba, Mazzini Letizia, Bellan Mattia, De Marchi Fabiola
Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.
AOU Maggiore Della Carità, Novara, Italy.
Mol Neurobiol. 2025 May;62(5):6273-6282. doi: 10.1007/s12035-024-04671-x. Epub 2025 Jan 6.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects the motor neurons in the brain and spinal cord. While the exact cause of ALS is not fully understood, a combination of genetic and environmental factors is believed to contribute to its development. Growth arrest-specific 6 (Gas6), a vitamin K-dependent protein, has been recognized to enhance oligodendrocytes and neurons' survival and is associated with different kinds of (neuro)inflammatory conditions. Therefore, we aimed to determine a possible implication of Gas6 in ALS phenotype and progression by evaluating the value of circulating Gas6 and its soluble receptors (sAxl, sMer, sTyro-3) in ALS patients. We conducted a prospective observational study including 65 ALS patients and measured the circulating serum levels of Gas6, sAxl, sMer, soluble Tyro-3 (sTyro-3), and neurofilaments (NfLs). In our ALS cohort, lower serum levels of Gas6 and concomitantly higher levels of NfLs were associated with a more aggressive disease, expressed with bulbar phenotype (p-value for Gas6 = 0.03) and faster progression (p-value for Gas6 = 0.03). Also, serum Gas6 was able to distinguish (area under the curve, cut-off 13.70 ng/mL, sensitivity 69.57%, specificity 72.72%) between fast and slow progressors. Due to its neuroprotective properties, our data suggest that Gas6 could be an intriguing biomarker in ALS patients.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病，主要影响大脑和脊髓中的运动神经元。虽然ALS的确切病因尚未完全明确，但据信遗传因素和环境因素共同作用导致了其发病。生长停滞特异性蛋白6（Gas6）是一种维生素K依赖性蛋白，已被证实可提高少突胶质细胞和神经元的存活率，并与多种（神经）炎症状态相关。因此，我们旨在通过评估ALS患者循环Gas6及其可溶性受体（sAxl、sMer、sTyro-3）的值，来确定Gas6在ALS表型和病情进展中的可能作用。我们进行了一项前瞻性观察研究，纳入65例ALS患者，测量了循环血清中Gas6、sAxl、sMer、可溶性Tyro-3（sTyro-3）和神经丝（NfLs）的水平。在我们的ALS队列中，较低的血清Gas6水平以及较高的NfLs水平与更具侵袭性的疾病相关，表现为延髓表型（Gas6的p值 = 0.03）和更快的病情进展（Gas6的p值 = 0.03）。此外，血清Gas6能够区分（曲线下面积，截断值13.70 ng/mL，敏感性69.57%，特异性72.72%）快速进展者和缓慢进展者。鉴于其神经保护特性，我们的数据表明Gas6可能是ALS患者中一个有趣的生物标志物。
