The number of genes associated with motor neuron degeneration has increased considerably over the past few years. As more gene mutations are identified, the hope arises that certain common themes and/or pathways become clear. In this overview, we focus on recent discoveries related to amyotrophic lateral sclerosis (ALS), spinal muscular atrophies (SMA), and distal hereditary motor neuropathies (dHMN). It is striking that many of the mutated genes that were linked to these diseases encode proteins that are either directly or indirectly involved in axonal transport or play a role in RNA metabolism. We hypothesize that both phenomena are not only crucial for the normal functioning of motor neurons, but that they could also be interconnected. In analogy with the situation after acute stress, axonal mRNA translation followed by retrograde transport of the signal back to the nucleus could play an important role in chronic motor neuron diseases. We hope that information on the genetic causes of these diseasesand the insight into the pathologic processes involved could ultimately lead to therapeutic strategies that prevent or at least slow this degenerative process.
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