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Amyloid‐beta ( A β 1–42 )‐induced paralysis in C aenorhabditis elegans is inhibited by the polyphenol quercetin through activation of protein degradation pathways
Author(s) -
Regitz Charlotte,
Marie Dußling Lisa,
Wenzel Uwe
Publication year - 2014
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201400014
Subject(s) - unfolded protein response , quercetin , endoplasmic reticulum , proteostasis , microbiology and biotechnology , autophagy , protein aggregation , protein degradation , small interfering rna , biology , caenorhabditis elegans , chemistry , rna interference , rna , biochemistry , apoptosis , antioxidant , gene
Scope Dietary polyphenols are suggested to play a role in the prevention of Alzheimer's disease, of which accumulation of aggregated beta amyloid (Aβ) is a key histopathological hallmark. We used the transgenic Caenorhabditis elegans strain CL 2006, which expresses human Aβ 1–42 under control of a muscle‐specific promoter and responds to Aβ 1–42 aggregation with paralysis, to test effects of the polyphenol quercetin on the phenotype. Methods and results Quercetin dose‐dependently decreased the amount of aggregated proteins in solution and also paralysis in CL 2006. The knockdown of key components of unfolded protein response in mitochondria or the endoplasmic reticulum by RNA ‐interference ( RNA i) enhanced paralysis in CL 2006 but did not prevent the paralysis reducing activities of quercetin. RNA i for essential members of proteasomal protein degradation or macroautophagy also significantly increased paralysis but prevented quercetin from being effective. Quercetin increased proteasomal activity and, moreover, enhanced the flow of proteins through the macroautophagy pathway as reflected by reduced lysosome staining. Conclusion The proteostasis network, including unfolded protein response, defines the aggregation of A β 1–42 and the associated paralysis phenotype in a nematode model for A lzheimer's disease. The polyphenol quercetin, by specifically activating macroautophagy and proteasomal degradation pathways, proved able to prevent Aβ 1–42 agregation and paralysis.