Blusch Alina, Björkqvist Maria
Wallenberg Neuroscience Center, Brain Disease Biomarker Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
J Huntingtons Dis. 2025 Aug;14(3):258-269. doi: 10.1177/18796397251338207. Epub 2025 Aug 7.
Huntington's disease (HD) is a progressive neurodegenerative disorder, and increasing evidence suggests that inflammation, both central and peripheral, plays a role in disease progression. Neurohistology and neuroimaging studies illustrate neuroinflammatory processes as part of HD pathophysiology. Furthermore, studies of blood and cerebrospinal fluid from HD patients show altered levels of inflammatory markers and immune cell populations that could influence neuroinflammation and the neurodegenerative process. Here, we review findings contributing to our understanding of the significance of immune activation in HD pathology. We discuss evidence of intrinsic effects of mutant huntingtin within immune cells and central immune alterations that contribute to neuroinflammation and neurodegeneration. We address the roles of central immune cells, as well as the potential contributions of peripheral signals and cell types in HD immune activation. We further discuss opportunities and challenges in utilizing immune-modulation strategies for future treatment approaches. A better understanding of neuroimmune interactions in HD can provide insights for manipulating these responses, potentially facilitating the development of therapies aimed at reducing the impact of neuroinflammatory and degenerative processes.
亨廷顿舞蹈症(HD)是一种进行性神经退行性疾病,越来越多的证据表明,中枢和外周的炎症在疾病进展中发挥作用。神经组织学和神经影像学研究表明,神经炎症过程是HD病理生理学的一部分。此外,对HD患者血液和脑脊液的研究显示,炎症标志物和免疫细胞群水平发生改变,这可能影响神经炎症和神经退行性过程。在此,我们回顾有助于我们理解免疫激活在HD病理学中意义的研究结果。我们讨论突变型亨廷顿蛋白在免疫细胞内的内在作用以及导致神经炎症和神经退行性变的中枢免疫改变的证据。我们阐述中枢免疫细胞的作用,以及外周信号和细胞类型在HD免疫激活中的潜在作用。我们还进一步讨论了利用免疫调节策略进行未来治疗的机遇和挑战。更好地理解HD中的神经免疫相互作用可为操控这些反应提供思路,有可能促进旨在减轻神经炎症和退行性过程影响的治疗方法的开发。