Tsachaki Maria, Ghiso Jorge, Efthimiopoulos Spiros
Division of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, Athens, Greece.
Biotechnol J. 2008 Dec;3(12):1548-54. doi: 10.1002/biot.200800247.
BRI2 is a protein that when mutated causes familial British and familial Danish dementias. Upon cleavage, the mutated BRI2 proteins release the peptides ABri and ADan, which are amyloidogenic and accumulate in the brains of patients. Although BRI2 has an unknown function, several reports indicate that it could play multiple roles. For example, the fact that it exists at the cell surface as a homodimer indicates that it could be involved in cell signaling events by acting as a receptor. BRI2 also interacts with amyloid precursor protein (APP), involved in Alzheimer's disease (AD). In cell cultures and mouse models of AD, BRI2 inhibits APP processing and reduces amyloid beta peptide deposition. The interaction between the two proteins could be responsible for the neuropathological similarities between familial British/Danish dementias and AD. The study of BRI2, which is central in familial British and Danish dementia, could unravel underlying molecular mechanisms of neurodegeneration.
BRI2是一种蛋白质，发生突变时会导致家族性英国痴呆症和家族性丹麦痴呆症。经切割后，突变的BRI2蛋白会释放出肽段ABri和ADan，这些肽段具有淀粉样变性，会在患者大脑中积累。尽管BRI2的功能尚不清楚，但一些报告表明它可能发挥多种作用。例如，它以同源二聚体的形式存在于细胞表面，这表明它可能通过充当受体参与细胞信号传导事件。BRI2还与参与阿尔茨海默病（AD）的淀粉样前体蛋白（APP）相互作用。在AD的细胞培养和小鼠模型中，BRI2抑制APP的加工并减少淀粉样β肽的沉积。这两种蛋白质之间的相互作用可能是家族性英国/丹麦痴呆症与AD之间神经病理学相似性的原因。对在家族性英国和丹麦痴呆症中起核心作用的BRI2的研究，可能会揭示神经退行性变的潜在分子机制。
