Dipartimento di Bioscienze, Università degli Studi di Milano, 20133 Milano, Italy.
Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, 20122 Milano, Italy.
Int J Mol Sci. 2020 Feb 21;21(4):1484. doi: 10.3390/ijms21041484.
Pathologies that lead to neurodegeneration in the central nervous system (CNS) represent a major contemporary medical challenge. Neurodegenerative processes, like those that occur in Alzheimer's disease (AD) are progressive, and at the moment, they are unstoppable. Not only is an adequate therapy missing but diagnosis is also extremely complicated. The most reliable method is the measurement of beta amyloid and tau peptides concentration in the cerebrospinal fluid (CSF). However, collecting liquid samples from the CNS is an invasive procedure, thus it is not suitable for a large-scale prevention program. Ideally, blood testing is the most manageable and appropriate diagnostic procedure for a massive population screening. Recently, a few candidates, including proteins or microRNAs present in plasma/serum have been identified. The aim of the present work is to propose the chloride intracellular channel 1 (CLIC1) protein as a potential marker of neurodegenerative processes. CLIC1 protein accumulates in peripheral blood mononuclear cells (PBMCs), and increases drastically when the CNS is in a chronic inflammatory state. In AD patients, both immunolocalization and mRNA quantification are able to show the behavior of CLIC1 during a persistent inflammatory state of the CNS. In particular, confocal microscopy analysis and electrophysiological measurements highlight the significant presence of transmembrane CLIC1 (tmCLIC1) in PBMCs from AD patients. Recent investigations suggest that tmCLIC1 has a very specific role. This provides an opportunity to use blood tests and conventional technologies to discriminate between healthy individuals and patients with ongoing neurodegenerative processes.
导致中枢神经系统（CNS）神经退行性变的病变是当代医学面临的主要挑战。神经退行性过程，如阿尔茨海默病（AD）中发生的过程，是进行性的，目前是不可阻挡的。不仅缺乏有效的治疗方法，而且诊断也极其复杂。最可靠的方法是测量脑脊液（CSF）中β淀粉样蛋白和tau 肽的浓度。然而，从 CNS 采集液体样本是一种侵入性程序，因此不适合大规模的预防计划。理想情况下，血液检测是大规模人群筛查最可行和最合适的诊断程序。最近，已经确定了一些候选物，包括存在于血浆/血清中的蛋白质或 microRNAs。本工作的目的是提出氯离子通道 1（CLIC1）蛋白作为神经退行性过程的潜在标志物。CLIC1 蛋白在周围血单核细胞（PBMC）中积累，当 CNS 处于慢性炎症状态时，其含量会急剧增加。在 AD 患者中，免疫定位和 mRNA 定量都能够显示 CNS 持续炎症状态下 CLIC1 的行为。特别是，共聚焦显微镜分析和电生理测量突出显示了 AD 患者 PBMC 中跨膜 CLIC1（tmCLIC1）的显著存在。最近的研究表明，tmCLIC1 具有非常特殊的作用。这为使用血液检测和常规技术来区分健康个体和正在进行神经退行性过程的患者提供了机会。
