National Research Council (CNR), Institute of Biomedical Technologies, Bari Unit, 70125 Bari, Italy.
Int J Mol Sci. 2023 Mar 28;24(7):6354. doi: 10.3390/ijms24076354.
The term "neurodegenerative diseases" (NDs) identifies a group of heterogeneous diseases characterized by progressive loss of selectively vulnerable populations of neurons, which progressively deteriorates over time, leading to neuronal dysfunction. Protein aggregation and neuronal loss have been considered the most characteristic hallmarks of NDs, but growing evidence confirms that significant dysregulation of innate immune pathways plays a crucial role as well. NDs vary from multiple sclerosis, in which the autoimmune inflammatory component is predominant, to more "classical" NDs, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. Of interest, many of the clinical differences reported in NDs seem to be closely linked to sex, which may be justified by the significant changes in immune mechanisms between affected females and males. In this review, we examined some of the most studied NDs by looking at their pathogenic and phenotypical features to highlight sex-related discrepancies, if any, with particular interest in the individuals' responses to treatment. We believe that pointing out these differences in clinical practice may help achieve more successful precision and personalized care.
“神经退行性疾病”（NDs）这一术语可识别出一组异质性疾病，其特征为选择性脆弱神经元群体的进行性丧失，随着时间的推移逐渐恶化，导致神经元功能障碍。蛋白聚集和神经元丧失被认为是 NDs 的最典型特征，但越来越多的证据证实，先天免疫途径的显著失调也起着至关重要的作用。NDs 包括多发性硬化症，其自身免疫炎症成分占主导地位，以及更“经典”的 NDs，如帕金森病、阿尔茨海默病、肌萎缩侧索硬化症和脊髓性肌萎缩症。有趣的是，在 NDs 中报告的许多临床差异似乎与性别密切相关，这可以通过受影响的女性和男性之间的免疫机制的显著变化来解释。在这篇综述中，我们研究了一些研究最多的 NDs，通过观察它们的发病机制和表型特征，来突出性别差异，如果有的话，特别关注个体对治疗的反应。我们认为，在临床实践中指出这些差异可能有助于实现更成功的精准和个性化护理。
