ALS, a cellular whodunit on motor neuron degeneration

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily targets motor neurons. Motor neurons from ALS patients show cytoplasmic inclusions that are reflective of an altered RNA metabolism and protein degradation. Causal gene mutations are found in all cell types even though patient motor neurons are by far the most susceptible to the degeneration. Using induced pluripotent stem cell (iPSC) technology, researchers have generated motor neurons with the same genotype as the patient including sporadic ones. They have also generated other cell types associated with the disease such as astrocytes, microglia and oligodendrocytes. These cells provide not only new insights on the mechanisms of the disease from the early stage, but also a platform for drug screening that has led to several clinical trials. This review examines the knowledge gained from iPSC studies using patient cells on the gene mutations and cellular networks in ALS and relevant experimental therapies.

Keywords: Amyotrophic lateral sclerosis; Clinical therapy; Drug repurposing; Induced pluripotent stem cell; Motor neurons; miRNA.