Bataveljic Danijela, Milosevic Milena, Radenovic Lidija, Andjus Pavle
Center for Laser Microscopy, Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski Trg 16, POB 52, 11000 Belgrade, Serbia.
Biomed Res Int. 2014;2014:907545. doi: 10.1155/2014/907545. Epub 2014 May 11.
Recently neuroinflammation has gained a particular focus as a key mechanism of ALS. Several studies in vivo as well as in vitro have nominated immunoglobulin G (IgG) isolated from ALS patients as an active contributor to disease onset and progression. We have shown that ALS IgG affects astroglial Ca(2+) excitability and induces downstream activation of phosphatidylinositol 3-kinase. These studies were hampered by a lack of knowledge of the pathway of entry of immune factors in the CNS. Our MRI data revealed the blood-brain barrier BBB leakage and T cell infiltration into brain parenchyma in ALS G93A rats. Since astrocyte ensheathes blood vessel wall contributing to BBB stability and plays an important role in ALS pathogenesis, we have studied astrocytic membrane proteins water channel aquaporin-4 and the inwardly rectifying potassium channel. In this review, we will summarize data related to BBB disruption with particular emphasis on impaired function of astrocytes in ALS. We will discuss implication of membrane proteins expressed on astrocytic endfeet, aquaporin-4, and inwardly rectifying potassium channel in the pathology of ALS. In addition to ALS-specific IgGs, these membrane proteins are proposed as novel biomarkers of the disease.
近年来，神经炎症作为肌萎缩侧索硬化症（ALS）的关键机制受到了特别关注。多项体内和体外研究表明，从ALS患者体内分离出的免疫球蛋白G（IgG）是疾病发生和进展的积极促成因素。我们已经证明，ALS IgG会影响星形胶质细胞的Ca(2+)兴奋性，并诱导磷脂酰肌醇3激酶的下游激活。这些研究因缺乏对免疫因子进入中枢神经系统途径的了解而受到阻碍。我们的MRI数据显示，在ALS G93A大鼠中存在血脑屏障（BBB）渗漏和T细胞浸润到脑实质中。由于星形胶质细胞包裹血管壁有助于BBB的稳定性，并且在ALS发病机制中起重要作用，我们研究了星形胶质细胞膜蛋白水通道蛋白4和内向整流钾通道。在这篇综述中，我们将总结与BBB破坏相关的数据，特别强调ALS中星形胶质细胞功能受损的情况。我们将讨论星形胶质细胞终足上表达的膜蛋白、水通道蛋白4和内向整流钾通道在ALS病理学中的意义。除了ALS特异性IgG外，这些膜蛋白被提议作为该疾病的新型生物标志物。
