To investigate the possible role of cyclin-dependent kinase 5 (cdk5) in the formation of paired helical filaments (PHFs) in muscle of patients with inclusion-body myositis (IBM), we immunolocalized cdk5, by light- and electron- microscopy, in muscle biopsies of six IBM patients. Approximately 80-90% of IBM vacuolated muscle fibers, and 10-15% of nonvacuolated fibers, contained well defined cdk5-immunoreactive inclusions that colocalized with phosphorylated tau in 70-80% of those fibers. Immunoelectronmicroscopy revealed the association of cdk5 with tau-immunoreactive PHFs. In all biopsies that contained them, regenerating muscle fibers had diffuse, moderate to strong cdk5 immunoreactivity. At all neuromuscular junctions, there was strong cdk5 immunoreactivity postsynaptically. Our study suggests that cdk5: (1) plays a role in IBM pathogenesis, possibly mediating phosphorylation of PHF-related tau; (2) is involved in muscle regeneration; and (3) has a novel function at normal neuromuscular junctions.

译文

为了研究细胞周期蛋白依赖性激酶5 (cdk5) 在包涵体肌炎 (IBM) 患者肌肉中成对螺旋细丝 (PHFs) 形成中的可能作用,我们通过光学和电子显微镜对cdk5进行了免疫定位。6名IBM患者的肌肉活检。大约80-90% 的IBM空泡肌肉纤维和10-15% 的非空泡纤维含有明确定义的cdk5-immunoreactive夹杂物,这些夹杂物与磷酸化的tau共定位在70-80% 的这些纤维中。免疫电镜显示cdk5与tau免疫反应性PHFs相关。在包含它们的所有活检中,再生肌纤维具有弥漫性,中度至强烈的cdk5免疫反应性。在所有神经肌肉连接处,突触后都有很强的cdk5免疫反应性。我们的研究表明cdk5 :( 1) 在IBM发病机理中起作用,可能介导PHF相关tau的磷酸化; (2) 参与肌肉再生; (3) 在正常神经肌肉连接处具有新的功能。

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