運動ニューロン疾患におけるGolgi装置の異常

Golgi apparatus of motor neurons in motor neuron diseases and in animal models

　はじめに

　Gonatasらは，Golgi装置（GA）を特異的に認識する抗MG160抗体を用いて，筋萎縮性側索硬化症（ALS）の脊髄前角細胞のGAに微細化（fragmentation）が高頻度に生じていることを報告した^9）。その後，ALSモデル動物の運動ニューロンにも同様の変化が生じていることが報告され，運動ニューロン疾患の変性過程におけるGAの関与が示唆されている^{9, 10）}。一方，表に示すように運動ニューロン疾患以外にもアルツハイマー病や多系統萎縮症，パーキンソン病などの神経変性疾患においてもGAの微細化がみられること^6,12），さらにGAの微細化とアポトーシスとの関連を示唆する報告もあり^{7, 8）}，GAの形態的変化の意義を明らかにすることは，疾患解明において有意義なことと考えられる。

　今回，これまで筆者らが免疫組織学的に検討した運動ニューロン疾患，およびALSモデル動物のGAの形態異常について報告する。

　Several reports demonstrated that Golgi apparatus（GA）of motor neurons in sporadic amyotrophic lateral sclerosis（ALS）showed fragmentation, where the GA were dispersed or fragmented into numerous small isolated elements. In our experiments, similar Golgi fragmentation was observed in motor neurons of the other motor neuron diseases（MND）and animal models of ALS, such as transgenic mice expressing G93 A mutation of the SOD1 gene, transgenic rats expressing two different mutations of SOD1 gene（G93 A and H46R）, Wobbler mice, and adult rats after facial nerve avulsion. Motor neurons in transgenic mice and rats showed fragmentation of the GA before the onset of paralysis. These findings suggest that the GA is an early target of the pathological processes that initiate neuronal degeneration. Furthermore, the GA in the majority of the motor neurons containing cytoplasmic inclusions, such as Bunina bodies, basophilic inclusions, and SOD1-positive-aggregates, were fragmented. Thus, we considered that abnormal proteinaceous cytoplasmic aggregates in MND were associated with the fragmented GA, which was involved in the chain of events leading to neuronal degeneration. The precise molecular mechanisms linking the aggregation of proteins and fragmentation of the GA are not known, and the identification of the molecular composition of the aggregated proteins remains a major challenge.