Publication date: Nov 27, 2019
Alterations in protein folding may lead to aggregation of misfolded proteins, which is strongly correlated with neurotoxicity and cell death. Protein aggregation has been shown as a normal consequence of aging, but it is largely associated with age-related disease, particularly neurodegenerative diseases like Huntington disease (HD). HD is caused by a CAG repeat expansion in the huntingtin gene and serves as a useful model for neurodegeneration due to its strictly genetic origin. Research in the model organism Caenorhabditis elegans suggests that glucose protects against cell stress, including proteotoxicity related to aggregation, despite the well-known, lifespan-shortening effects of glucose. We hypothesized that glucose could be beneficial by alleviating energy deficiency, a well-characterized phenomenon in HD. We used C. elegans expressing polyglutamine repeats to quantify lifespan, motility, reproduction, learning, and activity of succinate dehydrogenase (SDH), with and without glucose, to identify the role of glucose in proteotoxicity and neuroprotection. Our data show poly-Q worms on glucose plates exhibited shorter lifespans, no change in motility, learning, or SDH product formation, but had altered reproductive phenotypes. Notably, worms expressing toxic polyglutamine repeats were unable to learn association of food with a neutral odorant, even early in life.
Landon, G., Whitney, W., Priya, R., and Mindy, F. Glucose effects on polyglutamine-induced proteotoxic stress in Caenorhabditis elegans. 06807. 2019 Biochem Biophys Res Commun.
|drug||DRUGBANK||Dextrose unspecified form|
- Vildagliptin Attenuates Huntington’s Disease through Activation of GLP-1 Receptor/PI3K/Akt/BDNF Pathway in 3-Nitropropionic Acid Rat Model.