Toyoshima I, Sugawara M, Kato K, Wada C, Hirota K, Hasegawa K, Kowa H, Sheetz M P, Masamune O
Department of Internal Medicine, Akita University School of Medicine, Japan.
J Neurol Sci. 1998 Jul 15;159(1):38-44. doi: 10.1016/s0022-510x(98)00137-3.
Kinesin and cytoplasmic dynein are two major molecular motors responsible for fast axonal transport. As visualized by immunohistochemistry with monoclonal antibodies, both motors were found to be distributed throughout the cell bodies, dendrites and axons of motor neurons in normal human spinal cords. Large axonal swellings, spheroids, in the spinal cords of patients with motor neuron disease showed massive accumulation of kinesin co-localized with highly phosphorylated neurofilaments. Of 114 spheroids in five spinal cords, 87% were stained heavily with the three anti-kinesin antibodies used in this study. Cytoplasmic dynein was scarce or absent in most of the spheroids. These findings suggest that kinesin selectively accumulates in the spheroids of motor neuron axons, causing disturbance of the machinery for anterograde fast axonal transport in motor neuron disease.
驱动蛋白和胞质动力蛋白是负责快速轴突运输的两种主要分子马达。通过用单克隆抗体进行免疫组织化学观察发现,在正常人脊髓中,这两种马达蛋白均分布于运动神经元的整个细胞体、树突和轴突中。运动神经元疾病患者脊髓中的大轴突肿胀(即轴突球)显示,驱动蛋白大量积聚,并与高度磷酸化的神经丝共定位。在5个脊髓中的114个轴突球中,87%被本研究中使用的三种抗驱动蛋白抗体强烈染色。在大多数轴突球中,胞质动力蛋白稀少或缺失。这些发现表明,驱动蛋白选择性地积聚在运动神经元轴突的轴突球中,从而导致运动神经元疾病中顺向快速轴突运输机制的紊乱。