Ectoine and hydroxyectoine inhibit aggregation and neurotoxicity of Alzheimer's beta-amyloid.
beta-Amyloid peptide (Abeta) is the major constituent of senile plaques, the key pathological feature of Alzheimer's disease. Abeta is physiologically produced as a soluble form, but aggregation of Abeta monomers into oligomers/fibrils causes neurotoxic change of the peptide. In nature, many microorganisms accumulate small molecule chaperones (SMCs) under stressful conditions to prevent the misfolding/denaturation of proteins and to maintain their stability. Hence, it is conceivable that SMCs such as ectoine and hydroxyectoine could be potential inhibitors against the aggregate formation of Alzheimer's Abeta, which has not been studied to date. The current work shows the effectiveness of ectoine and hydroxyectoine on the inhibition of Abeta42 aggregation and toxicity to human neuroblastoma cells. The characterization tools used for this study include thioflavin-T induced fluorescence, atomic force microscopy and cell viability assay. Considering that ectoine and hydroxyectoine are not toxic to cellular environment even at concentrations as high as 100 mM, the results may suggest a basis for the development of ectoines as potential inhibitors associated with neurodegenerative diseases.
Kanapathipillai
Mathumai
M
Department of Chemical and Materials Engineering, Arizona State University, Tempe, AZ 85287, USA.
Lentzen
Georg
G
Sierks
Michael
M
Park
Chan Beum
CB
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000599:Amino Acids, Diamino / Q000737:chemistry / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D018625:Microscopy, Atomic Force; D015394:Molecular Structure; D009447:Neuroblastoma; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity*
D000599:Amino Acids, Diamino; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C121557:hydroxyectoine; C045628:ectoine