Compound I is an active oxidant responsible for the peroxidase activity of heme–Aβ and can cause oxidative degradation of neurotransmitters like serotonin, a marker of Alzheimer's disease.

The peroxidase activity of heme-Aβ can result in the oxidative degradation of neurotransmitters via a highly reactive high-valent intermediate, compound I.

The mononuclear copper hydroperoxo species (Cu(ii)–OOH) of Cu–Aβ is the active oxidant responsible for serotonin oxidation by Cu–Aβ in the presence of physiologically relevant oxidants like O2 and H2O2, which can potentially cause oxidative degradation of neurotransmitters, a marker of Alzheimer's disease.

Amyloids are protein aggregates bearing a highly ordered cross β structural motif, which may be functional but are mostly pathogenic. Their formation, deposition in tissues and consequent organ dysfunction is the central event in amyloidogenic diseases. Such protein aggregation may be brought about by conformational changes, and much attention has been directed toward factors like metal binding, post-translational modifications, mutations of protein etc., which eventually affect the reactivity and cytotoxicity of the associated proteins. Over the past decade, a global effort from different groups working on these misfolded/unfolded proteins/peptides has revealed that the amino acid residues in the second coordination sphere of the active sites of amyloidogenic proteins/peptides cause changes in H-bonding pattern or protein–protein interactions, which dramatically alter the structure and reactivity of these proteins/peptides. These second sphere effects not only determine the binding of transition metals and cofactors, which define the pathology of some of these diseases, but also change the mechanism of redox reactions catalyzed by these proteins/peptides and form the basis of oxidative damage associated with these amyloidogenic diseases. The present review seeks to discuss such second sphere modifications and their ramifications in the etiopathology of some representative amyloidogenic diseases like Alzheimer’s disease (AD), type 2 diabetes mellitus (T2Dm), Parkinson’s disease (PD), Huntington’s disease (HD), and prion diseases.

The heme(III)-Cu(i)-Aβ complexes relevant to Alzheimer’s disease (AD) can reduce nitrite to nitric oxide (NO) and thus behave as nitrite reductases.