Physical Sciences and Mathematics Commons^™

Amyloid Aggregation-Mitigating Peptides As Potential Alzheimer's Drugs, Cyrus Kipkurui Bett

LSU Doctoral Dissertations

Neuronal cytotoxicity observed in Alzheimer¡¦s disease (AD) is linked to the aggregation of £]-amyloid peptide (A£]) into toxic forms. Increasing evidence points to oligomeric species as the neurotoxic species compared to fibrils; disruption or inhibition of A£]ƒnself-assembly into oligomeric or fibrillar forms remains a viable therapeutic strategy to reduce A£] neurotoxicity. Amyloid aggregation mitigating peptides (AAMPs) were designed based on the A£]ƒn¡§hydrophobic core¡¨ A£]17-20, with C£\,£\-disubstituted amino acidsƒnƒv£\£\AAs) added into this core as disrupting agents. The number, distribution, and side chain functionality of £\£\AAs incorporated into the mitigator sequence was found influences the resultant aggregate morphology as indicated by ex-situ …