Department of Neurology, Medical Faculty Mannheim, MCTN, Heidelberg University , Mannheim, Germany.
Institute of Neuroanatomy, Medical Faculty Mannheim, MCTN, Heidelberg University , Mannheim, Germany.
Expert Opin Ther Targets. 2020 Dec;24(12):1211-1224. doi: 10.1080/14728222.2020.1842358. Epub 2020 Nov 8.
Multiple sclerosis (MS) is a chronic inflammatory-demyelinating disease of the central nervous system associated with lesions of the cortical gray matter and subcortical white matter. Recently, cortical lesions have become a major focus of research because cortical pathology and neuronal damage are critical determinants of irreversible clinical progression. Recent transcriptomic studies point toward cell type-specific changes in cortical neurons in MS with a selective vulnerability of excitatory projection neuron subtypes.
We discuss the cortical mapping and the molecular properties of excitatory projection neurons and their role in MS lesion pathology while placing an emphasis on their subtype-specific transcriptomic changes and levels of vulnerability. We also examine the latest magnetic resonance imaging techniques to study cortical MS pathology as a key tool for monitoring disease progression and treatment efficacy. Finally, we consider possible therapeutic avenues and novel strategies to protect excitatory cortical projection neurons. Literature search methodology: PubMed articles from 2000-2020.
Excitatory cortical projection neurons are an emerging therapeutic target in the treatment of progressive MS. Understanding neuron subtype-specific molecular pathologies and their exact spatial mapping will help establish starting points for the development of novel cell type-specific therapies and biomarkers in MS.
多发性硬化症（MS）是一种中枢神经系统的慢性炎症脱髓鞘疾病，与皮质灰质和皮质下白质的病变有关。最近，皮质病变已成为研究的主要焦点，因为皮质病理学和神经元损伤是不可逆临床进展的关键决定因素。最近的转录组学研究表明，MS 患者的皮质神经元存在特定于细胞类型的变化，兴奋性投射神经元亚型具有选择性易损性。
我们讨论了兴奋性投射神经元的皮质映射和分子特性及其在 MS 病变病理学中的作用，同时强调了它们的亚型特异性转录组变化和易损程度。我们还研究了最新的磁共振成像技术，以研究皮质 MS 病理学，作为监测疾病进展和治疗效果的关键工具。最后，我们考虑了可能的治疗途径和保护兴奋性皮质投射神经元的新策略。文献检索方法：从 2000 年到 2020 年，在 PubMed 上搜索文章。
兴奋性皮质投射神经元是治疗进行性 MS 的一个新兴治疗靶点。了解神经元亚型特异性的分子病理学及其确切的空间定位将有助于为 MS 中新型细胞类型特异性治疗和生物标志物的开发确定起点。
