Neuromuscular junction macromolecules in the pathogenesis of amyotrophic leteral sclerosis.

An hypothesis regarding the pathogenesis of amyotrophic lateral sclerosis is presented, which places emphasis on extraneural cells. Classical experimental denervation is compared and contrasted with motor neuron disease, both from information in the literature as well as concepts deriving from the hypothesis. Background information regarding neuromuscular junction-specific (16S) acetylcholinesterase and a basal lamina-enriched surface glycoprotein (fibronectin) are presented, which suggest not only their mutual interaction, but likely parallel regulation on muscle cell surfaces by the motor nerve. Since 16S acetylcholinesterase likely contains basal lamina-type collagen and fibronectin specifically associates with collagen, a model relating activation of latent collagenase enzyme in amyotrophic lateral sclerosis is described. It is suggested that continued degeneration, including transneuronal effects, of the motor system ensues from random, continuous loss of nerve-muscle adherence resulting from collagen resorption at the neuromuscular junction.