From Physiological Properties to Selective Vulnerability of Motor Units in Amyotrophic Lateral Sclerosis.

Abstract

Spinal alpha-motoneurons are classified in several types depending on the contractile properties of the innervated muscle fibers. This diversity is further displayed in different levels of vulnerability of distinct motor units to neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). We summarize recent data suggesting that, contrary to the excitotoxicity hypothesis, the most vulnerable motor units are hypoexcitable and experience a reduction in their firing prior to symptoms onset in ALS. We suggest that a dysregulation of activity-dependent transcriptional programs in these motoneurons alter crucial cellular functions such as mitochondrial biogenesis, autophagy, axonal sprouting capability and re-innervation of neuromuscular junctions.