Motor neurons derived from ALS-related mouse iPS cells recapitulate pathological features of ALS

Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain. Mutations in Cu/Zn superoxide dismutase 1 (SOD1) are known to induce ALS. Although many research models have been developed, the exact pathological mechanism of ALS remains unknown. The recently developed induced pluripotent stem (iPS) cell technology is expected to illuminate the pathological mechanisms and new means of treatment for neurodegenerative diseases. To determine the pathological mechanism of ALS, we generated mouse iPS (miPS) cells from experimental ALS transgenic mice and control mice and characterized the cells using molecular biological methods. The generated miPS cells expressed many pluripotent genes and differentiated into three germ layers in vitro and in vivo. Motor neurons derived from ALS-related miPS cells recapitulated the pathological features of ALS. The ALS-model motor neurons showed SOD1 aggregates, as well as decreased cell survival rate and neurite length compared with wild-type motor neurons. Our study will be helpful in revealing the mechanism of motor neuronal cell death in ALS. A motor neuron-based model of amyotrophic lateral sclerosis (ALS) could shed further light on the mechanisms of disease. Seongman Kang and colleagues at Korea University in Seoul have demonstrated that induced pluripotent stem cells generated from a mouse model of ALS can be differentiated into neurons that show many features of the disease. The authors produced motor neurons from mice expressing a mutated version of the human superoxide dismutase 1 (SOD1) gene which is associated with familial ALS. They found that the cells not only showed aggregates of SOD1 protein but also had a decreased survival rate and shorter neural outgrowths than control motor neurons. These findings highlight the potential of stem cell technologies to make cell types that can be used as models for diseases which are otherwise difficult to explore.