Amyotrophic lateral sclerosis as a spatiotemporal mislocalization disease: location, location, location

Spatiotemporal localization of signals is a fundamental feature impacting cell survival and proper function. The cell needs to respond in an accurate manner in both space and time to both intra- and intercellular environment cues. The regulation of this comprehensive process involves the cytoskeleton and the trafficking machinery, as well as local protein synthesis and ligand-receptor mechanisms. Alterations in such mechanisms can lead to cell dysfunction and disease. Motor neurons that can extend over tens of centimeters are a classic example for the importance of such events. Changes in spatiotemporal localization mechanisms are thought to play a role in motor neuron degeneration that occurs in amyotrophic lateral sclerosis (ALS). In this review we will discuss these mechanisms and argue that possible misregulated factors can lead to motor neuron degeneration in ALS.