2013/09/25 by Rachael A. Dunlop, Paul Alan Cox, Sandra Anne Banack +1 · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · #Amino Acid Enzymes and Metabolism #RNA regulation and disease #Metabolism and Genetic Disorders #Serine #Protein folding #Biochemistry #Chemistry #Amino acid #Protein aggregation
paper · pdf · doi:10.1371/journal.pone.0075376
openalex publication_date 2013/09/25 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
Mechanisms of protein misfolding are of increasing interest in the aetiology of neurodegenerative diseases characterized by protein aggregation and tangles including Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Lewy Body Dementia (LBD), and Progressive Supranuclear Palsy (PSP). Some forms of neurodegenerative illness are associated with mutations in genes which control assembly of disease related proteins. For example, the mouse sticky mutation sti, which results in undetected mischarging of tRNA(Ala) with serine resulting in the substitution of serine for alanine in proteins causes cerebellar Purkinje cell loss and ataxia in laboratory animals. Replacement of serine 422 with glutamic acid in tau increases the propensity of tau aggregation associated with neurodegeneration. However, the possibility that environmental factors can trigger abnormal folding in proteins remains relatively unexplored. We here report that a non-protein amino acid, β-N-methylamino-L-alanine (BMAA), can be misincorporated in place of L-serine into human proteins. We also report that this misincorporation can be inhibited by L-serine. Misincorporation of BMAA into human neuroproteins may shed light on putative associations between human exposure to BMAA produced by cyanobacteria and an increased incidence of ALS.