Kürten Kilian, Gude Anne-Christin, Christian Epplen Aimo Samuel, Stein Jan, Theiss Carsten, Matschke Veronika
Department of Cytology, Institute of Anatomy, Medical Faculty, Ruhr University Bochum, Bochum, Germany.
Neural Regen Res. 2023 Jan;18(1):150-154. doi: 10.4103/1673-5374.343883.
Impaired axonal transport has been observed in patients with amyotrophic lateral sclerosis (ALS) and in animal models, suggesting that transport proteins likely play a critical role in the pathological mechanism of ALS. Dysregulation of Kinesin-family-member 5α (Kif5α), a neuron-specific isoform of heavy chain kinesin family, has been described in several neurological disorders, in humans and animal models, including ALS. In this study, we determined Kif5α expression by gene sequencing, quantitative reverse transcription-polymerase chain reaction, and western blot assay in the cervical spinal cord of wobbler mice and immunofluorescence staining in dissociated cultures of the ventral horn. Further, we observed the distribution of Kif5α and mitochondria along motor neuronal branches by confocal imaging. Our results showed that Kif5α expression was greatly dysregulated in wobbler mice, which resulted in altered distribution of Kif5α along motor neuronal branches with an abnormal mitochondrial distribution. Thus, our results indicate that dysregulation of Kif5 and therefore abnormal transport in motor neuronal branches in this ALS model could be causative for several pathological findings at the cellular level, like misallocation of cytoskeletal proteins or organelles like mitochondria.
在肌萎缩侧索硬化症（ALS）患者和动物模型中已观察到轴突运输受损，这表明运输蛋白可能在ALS的病理机制中起关键作用。驱动蛋白家族成员5α（Kif5α）是重链驱动蛋白家族的一种神经元特异性异构体，在包括ALS在内的多种人类和动物模型的神经疾病中，其表达失调已有报道。在本研究中，我们通过基因测序、定量逆转录-聚合酶链反应和蛋白质免疫印迹法测定了摇摆小鼠颈脊髓中Kif5α的表达，并在腹角解离培养物中进行了免疫荧光染色。此外，我们通过共聚焦成像观察了Kif5α和线粒体沿运动神经元分支的分布。我们的结果表明，摇摆小鼠中Kif5α的表达严重失调，这导致Kif5α沿运动神经元分支的分布改变，线粒体分布异常。因此，我们的结果表明，在这个ALS模型中，Kif5的失调以及运动神经元分支中的异常运输可能是细胞水平上一些病理结果的原因，比如细胞骨架蛋白或线粒体等细胞器的错误分配。
