Most cases are sporadic and their causes are usually not known. It is thought that environmental, toxic, viral, or genetic factors may be involved. DNA damage TARDBP (TAR DNA-binding protein 43), also referred to as TDP-43, is a critical component of the non-homologous end joining (NHEJ) enzymatic pathway that repairs DNA double-strand breaks in pluripotent stem cell-derived<unk>  neurons. TDP-43 is rapidly recruited to double-strand breaks where it acts as a scaffold for the recruitment of the XRCC4-DNA ligase protein complex that then acts to repair double-strand breaks. About 95% of ALS patients have abnormalities in the nucleus-cytoplasmic localization in spinal<unk>  neurons of TDP43. In TDP-43 depleted human neural stem cell-derived<unk>  neurons, as well as in sporadic ALS patients’ spinal cord specimens there is significant double-strand break accumulation and reduced levels of NHEJ. Associated risk factors In adults, men are more commonly affected than women.
Motor neuron disease
Vascular myelopathy
Polyneuropathy
Basal ganglia disease
Upper motor neuron syndrome
Distal hereditary motor neuronopathies
Tropical ataxic neuropathy
Amyotrophic lateral sclerosis