ABSTRACT
The α-helical structure of the N-terminus of the 'native' amylin Lys1-Cys7 consists of a disulfide bond between Cys2 and Cys7. The 'native' amylin oligomers demonstrate polymorphic states. Removal of the disulfide bonds in the 'native' amylin oligomers decreases the polymorphism and induces the formation of longer stable cross-ß strands in the N-termini.
Subject(s)
Disulfides/chemistry , Islet Amyloid Polypeptide/chemistry , Protein Multimerization , Molecular Dynamics Simulation , Protein Structure, SecondaryABSTRACT
Evidence indicates that inflammation, oxidative stress, and the disruption of normal conformation of proteins might be directly linked to Alzheimer's disease (AD). The present study was undertaken using literature data to find a possible drug to address the multiple disorders involved in AD-associated Aß accumulation and plaque formation. We consider NOSH-aspirin a drug of choice for reducing the inflammatory areas in the brain (aspirin moiety), removing the noxious heavy metals from plaques (hydrogen sulfide), and increasing the oxygen supply to neurons since nitrogen oxide is a potent vasodilator and an anti-inflammatory agent. Several confirmatory data in literature and possible mechanisms for cellular defence as well as novel therapeutical pathways are discussed.
