Glial cells involvement in spinal muscular atrophy: Could SMA be a neuroinflammatory disease?

Abstract

Spinal muscular atrophy (SMA) is a severe, inherited disease characterized by the progressive degeneration and death of motor neurons of the anterior horns of the spinal cord, which results in muscular atrophy and weakness of variable severity. Its early-onset form is invariably fatal in early childhood, while milder forms lead to permanent disability, physical deformities and respiratory complications. Recently, two novel revolutionary therapies, antisense oligonucleotides and gene therapy, have been approved, and might prove successful in making long-term survival of these patients likely. In this perspective, a deep understanding of the pathogenic mechanisms and of their impact on the interactions between motor neurons and other cell types within the central nervous system (CNS) is crucial. Studies using SMA animal and cellular models have taught us that the survival and functionality of motor neurons is highly dependent on a whole range of other cell types, namely glial cells, which are responsible for a variety of different functions, such as neuronal trophic support, synaptic remodeling, and immune surveillance. Thus, it emerges that SMA is likely a non-cell autonomous, multifactorial disease in which the interaction of different cell types and disease mechanisms leads to motor neurons failure and loss. This review will introduce the different glial cell types in the CNS and provide an overview of the role of glial cells in motor neuron degeneration in SMA. Furthermore, we will discuss the relevance of these findings so far and the potential impact on the success of available therapies and on the development of novel ones.

Keywords

• Spinal muscular atrophy
• SMA
• Glia
• Neuroinflammation
• Astrocytes
• Microglia