Akiyama Haruhiko
Tokyo Institute of Psychiatry, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2006 Feb;26(1):23-31.
Many neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are now characterized by abnormal accumulation of certain proteins in the brain. The key molecules include amyloid beta-protein (Abeta), tau and a-synuclein, all of which are involved in the pathogenesis and provide histopathological hallmarks of the diseases. Abeta is continuously produced in and removed from the brain. Microglia and astrocytes take up and degrade soluble Abeta. In the Alzheimer brain, once-deposited, insoluble Abeta is also removed by phagocytosis by activated microglia. The success of these removal processes, however, is at best partial. The phagocytic removal of insoluble Abeta is associated with neuroinflammation, a potentially neurotoxic reaction. Tau is accumulated in astrocytes under a diversity of pathological conditions in several forms: thorn-shaped astrocytes; tuft-shaped astrocytes; astrocytic plaques. Thorn-shaped astrocytes are associated with gliosis and are not disease-specific. Tuft-shaped astrocytes are characteristic of progressive supranuclear palsy (PSP) and astrocytic plaques of cortico-basal degeneration (CBD). Tau accumulation in oligodendrocytes is referred to as coiled bodies and occurs in PSP, CBD, Pick's disease and some other so-called taupathies. a-Synuclein is accumulated in oligodendrocytes, which is referred to as glial cytoplasmic inclusions (GCI). Occurrence of GCI is diagnostic to multiple system atrophy. Transgenic mouse models in which tau or alpha-synuclein is overexpressed in glial cells indicate that neuronal degeneration occurs following tau/alpha-synuclein accumulation in glial cells, supporting a notion that these abnormal glial cells play pathogenic roles.
许多神经退行性疾病，如阿尔茨海默病和帕金森病，目前的特征是大脑中某些蛋白质异常积累。关键分子包括β-淀粉样蛋白（Aβ）、tau蛋白和α-突触核蛋白，所有这些都参与发病机制，并为疾病提供组织病理学特征。Aβ在大脑中持续产生并被清除。小胶质细胞和星形胶质细胞摄取并降解可溶性Aβ。在阿尔茨海默病大脑中，一旦沉积，不溶性Aβ也会被活化的小胶质细胞吞噬清除。然而，这些清除过程充其量只是部分成功。不溶性Aβ的吞噬清除与神经炎症有关，这是一种潜在的神经毒性反应。在多种病理条件下，tau蛋白以多种形式在星形胶质细胞中积累：棘状星形胶质细胞；簇状星形胶质细胞；星形胶质细胞斑块。棘状星形胶质细胞与胶质增生有关，并非疾病特异性。簇状星形胶质细胞是进行性核上性麻痹（PSP）的特征，而皮质基底节变性（CBD）则有星形胶质细胞斑块。少突胶质细胞中tau蛋白的积累被称为卷曲小体，见于PSP、CBD、匹克病和其他一些所谓的tau蛋白病。α-突触核蛋白在少突胶质细胞中积累，这被称为胶质细胞质包涵体（GCI）。GCI的出现对多系统萎缩具有诊断意义。在胶质细胞中过度表达tau或α-突触核蛋白的转基因小鼠模型表明，在胶质细胞中tau/α-突触核蛋白积累后会发生神经元变性，支持了这些异常胶质细胞起致病作用的观点。
