Decoding Conformational Imprint of Convoluted Molecular Interactions Between Prenylflavonoids and Aggregated Amyloid-Beta42 Peptide Causing Alzheimer's Disease

Protein misfolding occurs due to the loss of native protein structure and adopts an abnormal structure, wherein the misfolded proteins accumulate and form aggregates, which result in the formation of amyloid fibrils that are associated with neurodegenerative diseases. Amyloid beta (A beta 42) aggregation or amyloidosis is contemplated as a unique hallmark characteristic of Alzheimer's disease (AD). Due to aberrant accrual and aggregation of A beta 42 in extracellular space, the formation of senile plaques is found in AD patients. These senile plaques occur usually in the cognitive and memory region of the brain, enfeebles neurodegeneration, hinders the signaling between synapse, and disrupts neuronal functioning. In recent years, herbal compounds are identified and characterized for their potential as A beta 42 inhibitors. Thus, understanding their structure and molecular mechanics can provide an incredible finding in AD therapeutics. To describe the structure-based molecular studies in the rational designing of drugs against amyloid fibrils, we examined various herbal compounds that belong to prenylflavonoids. The present study characterizes the trends we identified at molecular docking studies and dynamics simulation where we observed stronger binding orientation of bavachalcone, bavachin, and neobavaisoflavone with the amyloid-beta (A beta 42) fibril structure. Hence, we could postulate that these herbal compounds could be potential inhibitors of A beta 42 fibrils; these anti-aggregation agents need to be considered in treating AD.

Automated summary

Protein misfolding leads to the formation of amyloid fibrils associated with neurodegenerative diseases like Alzheimer's disease. Herbal compounds have been identified as potential inhibitors of A beta 42 fibrils, offering a promising approach for AD treatment.