Aberrant protein folding and aggregation and increased vulnerability in motor neurons in ALS

Ooi L

  1. University of Wollongong, Wollongong, NSW 2522, Australia.
  2. Australia and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that causes the degeneration of motor neurons in the brain and spinal cord. The proteostasis network comprises pathways that regulate the biogenesis, folding, trafficking and degradation of proteins. The role of protein aggregates in the pathogenesis of ALS remains unclear. However misfolded and aggregated proteins contribute to a failure in proteostasis, which is thought to underlie motor neuron vulnerability in ALS. The aim of this research was to identify mechanisms underlying vulnerability of motor neurons in ALS. To address this we have used biochemical and electrophysiological tools to analyse motor neurons from induced pluripotent stem cells (iPSCs) from ALS patients, a SOD1G93A mouse model and post mortem tissue from ALS cases. We have identified alterations in membrane proteins, alterations in protein solubility and an increased vulnerability to cell stress in motor neurons in ALS. Further we have identified mechanisms that contribute to increased vulnerability and aberrant folding and aggregation of proteins in motor neurons in ALS.