Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
Department of Neurosciences, Azienda Ospedaliero-Universitaria di Modena, 41126 Modena, Italy.
Biomolecules. 2024 Aug 28;14(9):1076. doi: 10.3390/biom14091076.
Produced by the mitochondria and endoplasmic reticulum, neurosteroids such as allopregnanolone are neuroprotective molecules that influence various neuronal functions and regulate neuroinflammation. They are reduced in neurodegenerative diseases, while in the Wobbler mouse model, allopregnanolone and its precursor progesterone showed protective effects on motor neuron degeneration. This single-center case-control study included 37 patients with amyotrophic lateral sclerosis (ALS) and 28 healthy controls. Cerebrospinal fluid (CSF) neurosteroid levels were quantified using liquid chromatography-electrospray tandem mass spectrometry and compared between the two cohorts. Neurosteroid concentrations have been correlated with neuroinflammation and neurodegeneration biomarkers detected through an automated immunoassay, along with disease features and progression. Pregnenolone, progesterone, allopregnanolone, pregnanolone, and testosterone levels were significantly lower in ALS patients' CSF compared to healthy controls. A significant inverse correlation was found between neurofilament and neurosteroid levels. Neurosteroid concentrations did not correlate with disease progression, phenotype, genotype, or survival prediction. Our study suggests the independence of the disease features and its progression, from the dysregulation of neurosteroids in ALS patients' CSF. This neurosteroid reduction may relate to disease pathogenesis or be a consequence of disease-related processes, warranting further research. The inverse correlation between neurosteroids and neurofilament levels may indicate a failure of compensatory neuroprotective mechanisms against neurodegeneration.
由线粒体和内质网产生的神经甾体，如别孕烯醇酮，是具有神经保护作用的分子，影响各种神经元功能并调节神经炎症。它们在神经退行性疾病中减少，而在 wobbler 小鼠模型中，别孕烯醇酮及其前体孕酮对运动神经元变性表现出保护作用。这项单中心病例对照研究纳入了 37 名肌萎缩侧索硬化症（ALS）患者和 28 名健康对照者。采用液相色谱-电喷雾串联质谱法定量检测脑脊液（CSF）中的神经甾体水平，并比较两组之间的差异。神经甾体浓度与通过自动化免疫测定法检测到的神经炎症和神经退行性变生物标志物相关，并与疾病特征和进展相关。与健康对照组相比，ALS 患者的 CSF 中孕烯醇酮、孕酮、别孕烯醇酮、孕烷醇酮和睾酮水平显著降低。神经丝蛋白和神经甾体水平之间存在显著的负相关。神经甾体浓度与疾病进展、表型、基因型或生存预测无关。我们的研究表明，神经甾体在 ALS 患者 CSF 中的失调与疾病特征及其进展无关。这种神经甾体的减少可能与疾病发病机制有关，或者是疾病相关过程的结果，值得进一步研究。神经甾体和神经丝蛋白水平之间的负相关可能表明针对神经退行性变的代偿性神经保护机制失败。
