title: Is L-methionine a trigger factor for Alzheimer's-like neurodegeneration?: Changes in Aβ oligomers, tau phosphorylation, synaptic proteins, Wnt signaling and behavioral impairment in wild-type mice.
abstract: BACKGROUND
  L-methionine, the principal sulfur-containing amino acid in proteins, plays critical roles in cell physiology as an antioxidant and in the breakdown of fats and heavy metals. Previous studies suggesting the use of L-methionine as a treatment for depression and other diseases indicate that it might also improve memory and propose a role in brain function. However, some evidence indicates that an excess of methionine can be harmful and can increase the risk of developing Type-2 diabetes, heart diseases, certain types of cancer, brain alterations such as schizophrenia, and memory impairment.
  
  
  RESULTS
  Here, we report the effects of an L-methionine-enriched diet in wild-type mice and emphasize changes in brain structure and function. The animals in our study presented 1) higher levels of phosphorylated tau protein, 2) increased levels of amyloid-β (Aβ)-peptides, including the formation of Aβ oligomers, 3) increased levels of inflammatory response,4) increased oxidative stress, 5) decreased level of synaptic proteins, and 6) memory impairment and loss. We also observed dysfunction of the Wnt signaling pathway.
  
  
  CONCLUSIONS
  Taken together, the results of our study indicate that an L-methionine-enriched diet causes neurotoxic effects in vivo and might contribute to the appearance of Alzheimer's-like neurodegeneration.
authors.affiliation: Departamento de Biología Celular y Molecular; Facultad de Ciencias Biológicas, P. Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Cheril
authors.initials: C
authors.lastname: Tapia-Rojas
authors.affiliation: Departamento de Biología Celular y Molecular; Facultad de Ciencias Biológicas, P. Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Carolina B
authors.initials: CB
authors.lastname: Lindsay
authors.affiliation: Departamento de Biología Celular y Molecular; Facultad de Ciencias Biológicas, P. Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Carla
authors.initials: C
authors.lastname: Montecinos-Oliva
authors.affiliation: Departamento de Biología Celular y Molecular; Facultad de Ciencias Biológicas, P. Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Macarena S
authors.initials: MS
authors.lastname: Arrazola
authors.affiliation: Departamento de Biología Celular y Molecular; Facultad de Ciencias Biológicas, P. Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Rocio M
authors.initials: RM
authors.lastname: Retamales
authors.affiliation: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bunout
authors.affiliation: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hirsch
authors.affiliation: Departamento de Biología Celular y Molecular; Facultad de Ciencias Biológicas, P. Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago, Chile. ninestrosa@bio.puc.cl.|Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia. ninestrosa@bio.puc.cl.|Centro UC Síndrome de Down, Pontificia Universidad Católica de Chile, Santiago, Chile. ninestrosa@bio.puc.cl.|Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile. ninestrosa@bio.puc.cl.|CARE Biomedical Center, Pontificia Universidad Católica de Chile, Av. Alameda 340, Santiago, Chile. ninestrosa@bio.puc.cl.
authors.forename: Nibaldo C
authors.initials: NC
authors.lastname: Inestrosa
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D005260:Female; D008715:Methionine / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D060449:Wnt Signaling Pathway / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins; D008715:Methionine