In their struggle to understand the causes of amyotrophic lateral sclerosis (ALS), researchers have developed three theories over the years. Last week researchers added a fourth based on the role of VEGF in neuroprotection. The new theory doesn't suggest that the others are wrong, but rather builds a layer of detail onto the existing theories suggesting that manipulation of previously well characterized targets may have therapeutic value.

Current theories on the pathogenesis of ALS include the induction of neurodegeneration by oxidative damage to the cell; a role for glutamate excitotoxicity in motor neuron degeneration due to dysfunctional or mutated glutamate transporters in the CNS; and the theory that aggregates of misfolded or abnormal intracellular proteins, which are found in neurons from ALS patients, disrupt cellular function and induce apoptosis.