Monaco S, Autilio-Gambetti L, Zabel D, Gambetti P
Proc Natl Acad Sci U S A. 1985 Feb;82(3):920-4. doi: 10.1073/pnas.82.3.920.
Giant axonal neuropathies are a group of acquired and inherited human diseases morphologically characterized by accumulation of neurofilaments (NF) in enlargements of preterminal regions of central and peripheral axons. Slow axonal transport was studied in the optic systems of rats treated with 2,5-hexanedione, a toxic compound that produces an experimental model of giant axonal neuropathy. The transport rate of NF and of two other polypeptides of Mr 64,000 and 62,000 were selectively increased. Other components of the slow axonal transport were not affected. Acceleration of labeled NF was also observed when 2,5-hexanedione was given after [35S]methionine administration. Morphometric analysis revealed that the number of NF and the axon size were decreased in regions of optic axons proximal to the enlargements. It is suggested that acceleration of NF transport leads to a longitudinal redistribution of NF: NF decrease proximally and increase distally, forming NF-containing enlargements. Evidence was obtained that polypeptides of Mr 64,000 and 62,000 are cytoskeletal components related to intermediate filaments, normally migrating with the component a of the slow axonal transport. The 2,5-hexanedione axon may provide insight into the pathogenesis of inherited and acquired giant axonal neuropathies and offers a model to investigate the relationship between number of NF and axonal size in central axons.
巨大轴索性神经病是一组获得性和遗传性人类疾病，其形态学特征是神经丝（NF）在中枢和外周轴突终末前区域的膨大处积聚。在用2,5 -己二酮处理的大鼠视神经系统中研究了慢速轴突运输，2,5 -己二酮是一种能产生巨大轴索性神经病实验模型的有毒化合物。NF以及另外两种分子量为64,000和62,000的多肽的运输速率选择性增加。慢速轴突运输的其他成分未受影响。在给予[35S]甲硫氨酸后再给予2,5 -己二酮时，也观察到标记NF的加速运输。形态计量分析显示，在膨大近端的视神经轴突区域，NF数量和轴突大小均减少。提示NF运输加速导致NF的纵向重新分布：近端NF减少而远端增加，形成含NF的膨大。有证据表明，分子量为64,000和62,000的多肽是与中间丝相关的细胞骨架成分，通常与慢速轴突运输的a成分一起迁移。2,5 -己二酮处理的轴突可能有助于深入了解遗传性和获得性巨大轴索性神经病的发病机制，并提供一个模型来研究中枢轴突中NF数量与轴突大小之间的关系。
