Astrocytes in Motor Neuron Diseases.

Abstract

Motor neuron disorders are highly debilitating and mostly fatal conditions for which only limited therapeutic options are available. To overcome this limitation and develop more effective therapeutic strategies, it is critical to discover the pathogenic mechanisms that trigger and sustain motor neuron degeneration with the greatest accuracy and detail. In the case of Amyotrophic Lateral Sclerosis (ALS), several genes have been associated with familial forms of the disease, whilst the vast majority of cases develop sporadically and no defined cause can be held responsible. On the contrary, the huge majority of Spinal Muscular Atrophy (SMA) occurrences are caused by loss-of-function mutations in a single gene, SMN1. Although the typical hallmark of both diseases is the loss of motor neurons, there is increasing awareness that pathological lesions are also present in the neighbouring glia, whose dysfunction clearly contributes to generating a toxic environment in the central nervous system. Here, ALS and SMA are sequentially presented, each disease section having a brief introduction, followed by a focussed discussion on the role of the astrocytes in the disease pathogenesis. Such a dissertation is substantiated by the findings that built awareness on the glial involvement and how the glial-neuronal interplay is perturbed, along with the appraisal of this new cellular site for possible therapeutic intervention.