Effects of Vitamin BDeficiency on Amyloid-β Toxicity in.
Antioxidants (Basel). 2021 Jun 15 ;10(6). Epub 2021 Jun 15. PMID: 34203911
High homocysteine (Hcy) levels, mainly caused by vitamin Bdeficiency, have been reported to induce amyloid-β (Aβ) formation and tau hyperphosphorylation in mouse models of Alzheimer's disease. However, the relationship between Bdeficiency and Aβ aggregation is poorly understood, as is the associated mechanism. In the current study, we used the transgenicstrain GMC101, which expresses human Aβpeptides in muscle cells, to investigate the effects of Bdeficiency on Aβ aggregation-associated paralysis.GMC101 was grown on nematode growth medium with or without Bsupplementation or with 2--α-D-glucopyranosyl-L-ascorbic acid (AsA-2G) supplementation. The worms were age-synchronized by hypochlorite bleaching and incubated at 20 °C. After the worms reached the young adult stage, the temperature was increased to 25 °C to induce Aβ production. Worms lacking Bsupplementation exhibited paralysis faster and more severely than those that received it. Furthermore, supplementing B-deficient growth medium with AsA-2G rescued the paralysis phenotype. However, AsA-2G had no effect on the aggregation of Aβ peptides. Our results indicated that Bsupplementation lowered Hcy levels and alleviated Aβ toxicity, suggesting that oxidative stress caused by elevated Hcy levels is an important factor in Aβ toxicity.