Modulating Aβ Fibrillogenesis with ‘Trojan’ peptides

• Published in: Neuropeptides (Edinburgh) Vol. 81; p. 102030
• Main Authors: Pandey, Gaurav, Morla, Sudhir, Kumar, Sachin, Ramakrishnan, Vibin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.06.2020; Elsevier Science Ltd
• Subjects: Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid - antagonists & inhibitors; Amyloid - metabolism; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - metabolism; Amyloid-beta; Cell lines; Cytotoxicity; Fibrillogenesis; HEK293 Cells; Humans; Neurodegenerative diseases; Neuroimaging; Neurons - metabolism; Neurotoxicity; Peptide Biosynthesis; Peptide-based inhibitors; Peptides; Protein aggregation; Senile plaques; Trojan peptides; β-Amyloid; Protein aggregation; Peptide-based inhibitors; Trojan peptides; Amyloid-beta
• ISSN: 0143-4179; 1532-2785; 1532-2785
• DOI: 10.1016/j.npep.2020.102030

Abnormal aggregation of beta-amyloid (Aβ) peptide into amyloid plaques in the brain has been identified as one of the key factors in instigating AD pathogenesis. Inhibition of Aβ aggregation can be an important therapeutic strategy in disease management. In this work, we demonstrate the application of structure-based design of short peptides (‘trojan peptides’), intended to intervene in the aggregation of the core recognition domain of amyloid-beta peptide, a known malefactor in Alzheimer's disease. The modulatory effect of trojan peptides has been assessed using ThT fluorescence assay, FETEM imaging, IR, and toxicity assays on model neuronal cell lines. Experimental results suggest that designed trojan peptides could impede the aggregation of the core amyloid fibril forming segment of Aβ peptide, arrest the formation of toxic fibrillar assemblies, and reduce cytotoxicity of the neuronal cell lines. [Display omitted]