Neusch Clemens, Bähr Mathias, Schneider-Gold Christiane
Department of Neurology, University of Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Muscle Nerve. 2007 Jun;35(6):712-24. doi: 10.1002/mus.20768.
In classic neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), the pathogenic concept of a cell-autonomous disease of motor neurons has been challenged increasingly in recent years. Macro- and microglial cells have come to the forefront for their role in multistep degenerative processes in ALS and respective disease models. The activation of astroglial and microglial cells occurs early in the pathogenesis of the disease and seems to greatly influence disease onset and promotion. The role of oligodendrocytes and Schwann cells remains elusive. In this review we highlight the impact of nonneuronal cells in ALS pathology. We discuss diverse glial membrane proteins that are necessary to control neuronal activity and neuronal cell survival, and summarize the contribution of these proteins to motor neuron death in ALS. We also describe recently discovered glial mechanisms that promote motor neuron degeneration using state-of-the-art genetic mouse technology. Finally, we provide an outlook on the extent to which these new pathomechanistic insights may offer novel therapeutic approaches.
在诸如肌萎缩侧索硬化症（ALS）等经典神经退行性疾病中，运动神经元细胞自主性疾病的致病概念近年来受到了越来越多的挑战。巨噬细胞和小胶质细胞因其在ALS及相关疾病模型的多步退行性过程中的作用而成为研究焦点。星形胶质细胞和小胶质细胞的激活在疾病发病机制早期就会出现，并且似乎对疾病的发生和进展有很大影响。少突胶质细胞和施万细胞的作用仍不明确。在这篇综述中，我们强调了非神经元细胞在ALS病理学中的影响。我们讨论了控制神经元活动和神经元细胞存活所必需的多种胶质细胞膜蛋白，并总结了这些蛋白对ALS中运动神经元死亡的作用。我们还描述了最近利用先进的基因小鼠技术发现的促进运动神经元变性的胶质细胞机制。最后，我们展望了这些新的病理机制见解在多大程度上可能提供新的治疗方法。
