LAUSR

AIMS Alzheimer's disease is a neurodegenerative disease for which no cure is available. The presence of amyloid plaques in the extracellular space of neural cells is the key feature of this fatal disease. BACKGROUND The proteolysis of Amyloid Precursor Protein by presenilin leads to the formation of Amyloid-beta peptides (Aβ 42/40). Deposition of 42 residual Aβ peptides forms fibril's structure, disrupting neuron synaptic transmission, inducing neural cell toxicity, and ultimately leading to neuron death. OBJECTIVE Various novel peptides have been investigated via molecular docking and molecular dynamic simulation studies to investigate their effects on Aβ amyloidogenesis. METHOD The sequence-based peptides were rationally designed and investigated for their interaction with Aβ42 monomer and fibril, and their influence on the structural stability of target proteins was studied. RESULT Analyzed docking results suggest that the peptide YRIGY (P6) has the highest binding affinity with Aβ42 fibril amongst all the synthetic peptides, and the peptide DKAPFF (P12) similarly shows a better binding with the Aβ42 monomer. Moreover, simulation results also suggest that the higher the binding affinity, the better the inhibitory action. CONCLUSION These findings indicate that both the rationally designed peptides can modulate amyloidogenesis, but peptide (P6) has better potential for the disaggregation of the fibrils. In contrast, peptide P12 stabilizes the native structure of the Aβ42 monomer more effectively and hence can serve as a potential amyloid inhibitor. Thus, these peptides can be explored as therapeutic agents against Alzheimer's disease. Experimental testing of these peptides for immunogenicity, stability in cellular conditions, toxic effects and membrane permeability can be the future research scope of this study.