Targeting amyloidogenic proteins through cyclic peptides – A medicinal chemistry perspective

Abstract

Alzheimer’s Disease (AD) is characterized by the formation of amyloid-β (Aβ) in the extracellular region, neurofibrillary tangles (NFTs) in the intracellular region accompanied with neuroinflammation and decreased neurotransmitters in various regions of brain leading to neuroinflammation and neurodegeneration. Of the various bioactive molecules, Cyclic Peptides (CPs) are small circular chains of amino acids that can alter the structure and function of the proteins they interact with. They can be synthesized using chemical or genetic approach leading to the generation of diverse libraries of CPs that are screened for binding with desired target proteins. In AD, CPs can interfere at various levels, by either imitating the structure or altering the conformation of amyloidogenic proteins. They can also interfere with signal transduction by competing with amyloid proteins for various receptors which are involved in AD pathology. This review highlights the application of CPs as scaffolds for the identification of novel small molecules that can interfere with amyloid aggregation or for the formulation of vaccination against AD. Other proteins involved in the pathophysiological pathways of AD that can potentially be targeted for CP design have also been discussed.