An explanation for the changes in collagen in sporadic amyotrophic lateral sclerosis.

There is evidence showing abnormalities in collagen from the skin of patients with sporadic Amyotrophic Lateral Sclerosis (sALS) both from Guam and elsewhere. The non-proteinogenic amino acid beta-N-methylamino-L-alanine (BMAA) was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam, and has been implicated as a potential environmental factor in ALS and other neurodegenerative diseases. BMAA has a number of toxic effects on motor neurons including direct agonist action on NMDA and AMPA receptors, induction of oxidative stress, and depletion of glutathione. As a non-proteinogenic amino acid, there is also the strong possibility that BMAA could cause intraneuronal protein misfolding, the hallmark of neurodegeneration. While an animal model for BMAA-induced ALS is lacking, there is substantial evidence to support a link between this toxin and ALS. We hypothesize that the abnormalities seen in sALS collagen may result from the misincorporation of BMAA and subsequent misfolding of the collagen protein.