title: An explanation for the changes in collagen in sporadic amyotrophic lateral sclerosis.
abstract: 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.
authors: Department of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. nicholas.c.field@dartmouth.edu
authors: Nicholas C
authors: NC
authors: Field
authors: Tracie A
authors: TA
authors: Caller
authors: Elijah W
authors: EW
authors: Stommel
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D006141:Guam / Q000453:epidemiology; D006801:Humans; D017510:Protein Folding
chemical_list: D003094:Collagen