Ruffoli Riccardo, Biagioni Francesca, Busceti Carla L, Gaglione Anderson, Ryskalin Larisa, Gambardella Stefano, Frati Alessandro, Fornai Francesco
Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
I.R.C.C.S. Neuromed, Pozzilli, Isernia, Italy.
Histol Histopathol. 2017 Nov;32(11):1115-1123. doi: 10.14670/HH-11-895. Epub 2017 Apr 11.
Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.
肌萎缩侧索硬化症（ALS）通常由中枢神经系统中运动神经元的丧失所定义。因此，几十年来的形态学分析都将（皮质、脑干和脊髓中的）运动神经元视为选择性参与ALS的神经元群体。同样，这也被认为是在患者和实验模型中对疾病严重程度进行体外评分的病理标志物。然而，非自主性运动神经元死亡的概念最近被用来表明在ALS中需要其他细胞类型来导致运动神经元死亡。这意味着运动神经元的丧失仅在它们与其他细胞类型连接时才会发生。这个概念最初强调了驻留神经胶质细胞以及非驻留炎症细胞的必要性。如今，在导致非自主性运动神经元死亡的情况中，除运动神经元之外的其他神经元的额外作用也显现出来。事实上，在ALS中涉及到与运动神经元不同的神经元。这些细胞在ALS中发挥多种作用：（i）它们参与导致运动神经元丧失的一系列事件；（ii）它们甚至可能比运动神经元更早且更严重地退化。在本手稿中，讨论了关于ALS患者和实验模型中多神经元参与的证据。据报道，整个脊髓中特定的神经元亚类会退化或触发神经元退化，从而将ALS描绘为一种全脊髓疾病，而非仅仅影响运动神经元的疾病。这与运动神经元疾病中的一个新概念相关，该概念引入了细胞间通信的异常机制。
