De Marchi Fabiola, Munitic Ivana, Vidatic Lea, Papić Eliša, Rački Valentino, Nimac Jerneja, Jurak Igor, Novotni Gabriela, Rogelj Boris, Vuletic Vladimira, Liscic Rajka M, Cannon Jason R, Buratti Emanuele, Mazzini Letizia, Hecimovic Silva
Department of Neurology and ALS Centre, University of Piemonte Orientale, Maggiore Della Carità Hospital, Corso Mazzini 18, 28100 Novara, Italy.
Laboratory for Molecular Immunology, Department of Biotechnology, University of Rijeka, R. Matejcic 2, 51000 Rijeka, Croatia.
Biomedicines. 2023 Oct 14;11(10):2793. doi: 10.3390/biomedicines11102793.
Many potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases, such as Alzheimer's (AD) disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), as well as in a seemingly distinct Niemann-Pick type C disease with primarily juvenile onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets, such as microglia, peripheral macrophages, and regulatory T cells (Tregs); the complement system; and other soluble factors. In this review, we compare these neurodegenerative diseases from a clinical point of view and highlight common pathways and mechanisms of protein aggregation, neurodegeneration, and/or neuroinflammation that could potentially lead to shared treatment strategies for overlapping immune dysfunctions in these diseases. These approaches include but are not limited to immunisation, complement cascade blockade, microbiome regulation, inhibition of signal transduction, Treg boosting, and stem cell transplantation.
许多潜在的免疫治疗靶点在成人起病的神经退行性疾病中同样受到影响，如阿尔茨海默病（AD）、帕金森病（PD）、肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD），以及一种看似不同的主要为青少年起病的尼曼-匹克C型病。这有力地证明了致病机制存在重叠。常见的研究免疫靶点包括各种免疫细胞亚群，如小胶质细胞、外周巨噬细胞和调节性T细胞（Tregs）；补体系统；以及其他可溶性因子。在本综述中，我们从临床角度比较这些神经退行性疾病，并强调蛋白质聚集、神经退行性变和/或神经炎症的共同途径和机制，这些可能会为这些疾病中重叠的免疫功能障碍带来共同的治疗策略。这些方法包括但不限于免疫疗法、补体级联阻断、微生物群调节、信号转导抑制、Treg增强和干细胞移植。
