Amyotrophic lateral sclerosis (ALS) is a fatal devastating
neurodegenerative disorder which predominantly affects the motor neurons in the brain and spinal cord. The death of the motor neurons in ALS causes subsequent
muscle atrophy,
paralysis and eventual death. Clinical and
biological evidence now demonstrates that ALS has many similarities to
prion disease in terms of disease onset, phenotype variability and progressive spread. The pathognomonic ubiquitinated inclusions deposited in the neurons and glial cells in brains and spinal cords of patients with ALS and fronto-temporal lobar degeneration with ubiquitinated inclusions contain aggregated transactive response
DNA binding protein of 43 kDa (TDP-43), and evidence now suggests that TDP-43 has cellular
prion-like properties. The cellular mechanisms of
prion protein misfolding and aggregation are thought to be responsible for the characteristics of
prion disease. Therefore, there is a strong mechanistic basis for a
prion-like behaviour of the TDP-43
protein being responsible for some characteristics of ALS. In this review, we compare the
prion-like mechanisms of TDP-43 to the clinical and
biological nature of ALS in order to investigate how this
protein could be responsible for some of the characteristic properties of the disease.