Division of Pharmaceutical Sciences, University of Wisconsin, Madison, Wisconsin 53705, USA.
Neurotherapeutics. 2010 Oct;7(4):471-81. doi: 10.1016/j.nurt.2010.05.012.
Amyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by the progressive loss of motor neurons. Although the molecular mechanism underlying motor neuron degeneration remains unknown; non-neuronal cells (including astrocytes) shape motor neuron survival in ALS. Astrocytes closely interact with neurons to provide an optimized environment for neuronal function and respond to all forms of injury in a typical manner known as reactive astrogliosis. A strong reactive astrogliosis surrounds degenerating motor neurons in ALS patients and ALS-animal models. Although reactive astrogliosis in ALS is probably both primary and secondary to motor neuron degeneration; astrocytes are not passive observers and they can influence motor neuron fate. Due to the important functions that astrocytes perform in the central nervous system; it is of key importance to understand how these functions are altered when astrocytes become reactive in ALS. Here; we review the current evidences supporting a potential toxic role of astrocytes and their viability as therapeutic targets to alter motor neuron degeneration in ALS.
肌萎缩侧索硬化症(ALS)是一种致命的疾病,其特征是运动神经元的进行性丧失。尽管运动神经元退化的分子机制尚不清楚,但非神经元细胞(包括星形胶质细胞)在 ALS 中塑造运动神经元的存活。星形胶质细胞与神经元密切相互作用,为神经元功能提供优化的环境,并以典型的反应性星形胶质增生的方式对所有形式的损伤做出反应。在 ALS 患者和 ALS 动物模型中,退变的运动神经元周围存在强烈的反应性星形胶质增生。尽管 ALS 中的反应性星形胶质增生可能是运动神经元退化的原发性和继发性的,但星形胶质细胞并不是被动的观察者,它们可以影响运动神经元的命运。由于星形胶质细胞在中枢神经系统中发挥着重要的功能,因此了解当星形胶质细胞在 ALS 中变得反应性时这些功能如何发生改变是至关重要的。在这里,我们回顾了支持星形胶质细胞潜在毒性作用及其作为治疗靶点的证据,以改变 ALS 中的运动神经元退化。