Spinal muscular atrophy (SMA) is the most common genetically inherited
neurodegenerative disease resulting in infant mortality. SMA is caused by genetic deletion or
mutation in the survival of motor neuron 1 (SMN1) gene, which results in reduced levels of
the survival of motor neuron (SMN) protein. SMN protein deficiency preferentially affects α-
motor neurons, leading to their degeneration and subsequent atrophy of limb and trunk
muscles, progressing to death in severe forms of the disease. More recent studies have
shown that SMN protein depletion is detrimental to the functioning of other tissues including
skeletal muscle, heart, autonomic and enteric nervous systems, metabolic/endocrine (e.g.
pancreas), lymphatic, bone and reproductive system. In this review, we summarize studies
discussing SMN protein’s function in various cell and tissue types and their involvement in
the context of SMA disease etiology. Taken together, these studies indicate that SMA is a
multi-organ disease, which suggests that truly effective disease intervention may require
body-wide correction of SMN protein levels.
Keywords: Gene therapy, motor neuron, neuromuscular disease, spinal muscular atrophy, survival of motor
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