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

Molecular Neurodegeneration

Nibaldo C. Inestrosa²  Sandra Hirsch¹  Daniel Bunout¹  Rocio M. Retamales³  Macarena S. Arrazola³  Carla Montecinos-Oliva³  Carolina B. Lindsay³  Cheril Tapia-Rojas³ 

[1] Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile;CARE Biomedical Center, Pontificia Universidad Católica de Chile, Av. Alameda 340, Santiago, Chile;Departamento de Biología Celular y Molecular; Facultad de Ciencias Biológicas, P. Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago, Chile

关键词: Alzheimer’s disease;    Memory impairment;    Tau;    Amyloid;    L-Methionine;   

Others  :  1233611
DOI  :  10.1186/s13024-015-0057-0

 received in 2014-11-12, accepted in 2015-11-02,  发布年份 2015

【 摘 要 】

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 studypresented 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.

Conclusion

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.

【 授权许可】

   
2015 Tapia-Rojas et al.

【 图 表 】

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