Amyotrophic lateral sclerosis: A glial perspective

The lack of effective disease-modifying therapies for the treatment of Amyotrophic Lateral Sclerosis (ALS) demands for major research investments aimed at investigating novel mechanistic hypotheses as well as at validating unprecedented cellular and molecular targets for therapeutic intervention. Within this framework, glial cells have recently acquire great importance in view of the growing body of evidence indicating that motor neuron degeneration involves non-cell autonomous mechanisms in ALS, including the interaction with various glial cell populations. These observations not only have drawn attention to the physiopathological changes glial cells undergo during ALS progression, but they have moved the focus of the investigations beyond the neuronal compartment towards glia-neuron interactions. With this in mind, in this chapter, we dissect the specific contribution of the different glial subtypes to the dreadful chain of events leading to motor neuron sufferance and death in various forms of ALS. Furthermore, we discuss the possibility of targeting specific molecular defects in glial cell physiology and glia-neuron communication for the treatment of this disorder.