Role of Biomolecule Cues in Alzheimer’s disease

[摘要] The master’s thesis study investigates the role of biomolecules in Alzheimer’s disease.Alzheimer’s disease is caused by amyloid plaques and neurofibrillary tangles. The major cause of amyloid plaques is the aggregation of 1-42 amino acid peptide (abeta) fragment of the amyloid precursor protein. Neurofibrillary tangles on the other hand, are caused predominantly by the aggregation of microtubule binding hexapeptide (VQIVYK) region of the tau protein. The plaques and tangles ultimately cause neuronal cell toxicity, leading to Alzheimer’s disease. Several factors are known to cause abeta and tau aggregation. Here in this study, we investigate the effect of biomolecules on the aggregation formation of abeta and tau peptides, and test the potential of macromolecules, small molecules, and nanotherapeutics on the inhibition of abeta and tau peptides aggregation. The objective of the thesis study is achieved by investigating the role of (i) glycosaminoglycans (ii) extracellular enzymes transglutaminase and lysyl oxidase, and (iii) cerebral proteins transferrin and human albumin in Alzheimer’s causing peptides abeta and tau aggregation and toxicity. Characterization tools used for this study include biochemical assays, transmission electron microscopy, confocal microscopy, atomic force microscopy, dynamic light scattering, and cellular assays. The thesis study reveals that, glycosaminoglycans, and extracellular enzymes promote the aggregation of tau and abeta peptides, while cerebral proteins prevent the aggregation. Further, results show that the effect of biomolecules mediated Alzheimer’s peptide aggregation and could be inhibited in the presence of macromolecules, small molecules, and nanoformulated cerebral proteins.

[发布机构] University of Michigan

[效力级别] Alzheimers

[关键词] Protein;Alzheimers;Aggregation;Amyloid;Tau;Glycosaminoglycans;Biomedical engineering;Bioengineering, College of Engineering & Computer Science