the role of molecular chaperones in α-synuclein-related diseases

14-3-3蛋白是一种新型的分子伴侣，它识别多种靶蛋白的含磷酸丝氨酸的基序，并调节多种类型的信号转导途径。我们已经报道了14-3-3免疫反应性定位于帕金森病和多系统萎缩脑中含有α-突触核蛋白的包涵体。我们随后对人α-synuclein（A53 T）转基因小鼠的脑和脊髓进行了检测，发现α-synuclein和14-3-3蛋白在免疫组织化学上共定位。我们还观察到一些热休克蛋白在突触核蛋白病脑中的免疫反应性增加。此外，我们进行了14-3-3蛋白的免疫组织化学研究，从肌萎缩侧索硬化症（ALS）患者的尸检脊髓，发现14-3-3免疫反应在路易体样透明包涵体从散发性和家族性ALS病例。我们还观察到14-3-3免疫反应性定位于人SOD 1（G93 T）致伤小鼠前角细胞中含α-synuclein的包涵体蛋白。此外，我们发现14-3-3在多发性硬化和进行性多灶性白质脑病患者的脱髓鞘病变中，在克雅氏病患者的皮质和皮质下病变中，以及在宾斯旺格病病例的缺血性白色病变中的星形胶质细胞免疫表达增强。这些数据表明，14-3-3蛋白可能在神经退行性疾病的脑中几种类型的包涵体的形成中起重要作用，并且14-3-3蛋白可能在各种病理条件下，包括脱髓鞘、炎症和缺血，在星形胶质细胞中被诱导，并且可能与星形胶质细胞增生的形成有关。

14-3-3 proteins, a novel type of molecular chaperons, recognizes the phosphoserine-containing motifs of several target proteins, and regulates various types of signal transduction pathways. We have already reported that 14-3-3 immunoreactivity was localized to the α-synuclein-containing inclusins in brains with Parkinso's disease and multiple system atrophy. We then examined the brains and spinal cords of human α-synuclein (A53T) transgenic mice, and found the immunohistochemical colocalization of α-synuclein and 14-3-3 proteins. We also observed the increased immunoreactivities for some heat shock proteins in brains with synucleinopathies. Furthermore, we performed immunohistochemical studies on 14-3-3 proteins using autopsied spinal cord from patients with amyotrophic lateral sclerosis (ALS), and found 14-3-3 immunoreactivity in the Lewy body-like hyaline inclusions from both sporadic and familial ALS cases. We also observed that 14-3-3 immunoreactivity was localized to the α-synuclein-containing inclusinsin in the anterior horn cells from human SOD1(G93T) trausgenic mice. Moreover, we found the enhanced astroglial immunoexpression of 14-3-3 in the demyelinated lesions from patients with multiple sclerosis and progressive multifocal leukoencephalopathy, and in the cortical and subcortical lesions from patients with Creutzfeldt-Jakob disease, and in the ischemic white matter lesions from Binswanger's disease cases. These data suggest that 14-3-3 proteins may play an important role in the formation of several types of inclusions in brains with neurodegenerative diseases, and that 14-3-3 proteins may be induced in astrocytes under various kinds of pathological conditions, including demyelination, inflammation, and ischemia, and may be associated with the formation of astrogliosis.