Inhibition of beta-amyloid peptide aggregation and neurotoxicity by alpha-d-mannosylglycerate, a natural extremolyte.
The aggregation of soluble beta-amyloid (Abeta) peptide into oligomers/fibrils is one of the key pathological features in Alzheimer's disease (AD). The use of naturally occurring small molecules for inhibiting protein aggregation has recently attracted many interests due to their effectiveness for treating protein folding diseases such as AD, Parkinson's, Huntington's disease, and other amyloidosis diseases. alpha-d-Mannosylglycerate (MG), a natural extremolyte identified in microorganisms growing under extremely high temperatures up to 100 degrees C, had been shown to protect proteins against various stress conditions such as heat, freezing, thawing, and drying. Here, we report the effectiveness of MG on the suppression of Alzheimer's Abeta aggregation and neurotoxicity to human neuroblastoma cells. According to our study--carried out by using thioflavin-T induced fluorescence, atomic force microscopy, and cell viability assay--MG had significant inhibitory effect against Abeta amyloid formation and could reduce the toxicity of amyloid aggregates to human neuroblastoma cells while MG itself was innocuous to cells. On the other hand, the structural analogs of MG such as alpha-d-mannosylglyceramide, mannose, methylmannoside, glycerol, showed negligible effect on Abeta aggregate formation. The results suggest that MG could be a potential drug candidate for treating Alzheimer's disease.
Ryu
Jungki
J
Institute for the Bio-Century and Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 373-1 Guseong-dong, Yuseong-gu, Daejeon, Republic of Korea.
Kanapathipillai
Mathumai
M
Lentzen
Georg
G
Park
Chan Beum
CB
D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity / Q000648:ultrastructure; D002478:Cells, Cultured; D005988:Glyceric Acids / Q000494:pharmacology*; D006801:Humans; D008358:Mannose / Q000031:analogs & derivatives* / Q000494:pharmacology; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity / Q000648:ultrastructure
D016229:Amyloid beta-Peptides; D005988:Glyceric Acids; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C402688:mannosylglycerate; D008358:Mannose