Heme-Aβ in SDS micellar environment: Active site environment and reactivity.

Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disorder that causes brain cell death. Oxidative stress derived from the accumulation of redox cofactors like heme in amyloid plaques originating from amyloid β (Aβ) peptides has been implicated in the pathogenesis of AD. In the past our group has studied the interactions and reactivities of heme with soluble oligomeric and aggregated forms of Aβ. In this manuscript we report the interaction of heme with Aβ that remains membrane bound using membrane mimetic SDS (sodium dodecyl sulfate) micellar medium. Employing different spectroscopic techniques viz. circular dichroism (CD), absorption (UV-Vis), electron paramagnetic resonance (EPR) and resonance Raman (rR) we find that Aβ binds heme using one of its three His (preferentially His13) in SDS micellar medium. We also find that Arg5 is an essential distal residue responsible for higher peroxidase activity of heme bound Aβ in this membrane mimetic environment than free heme. This peroxidase activity exerted by even membrane bound heme-Aβ can potentially be more detrimental as the active site remains close to membranes and can hence oxidise the lipid bilayer of the neuronal cell, which can induce cell apoptosis. Thus, heme-Aβ in solution as well as in membrane-bound form are detrimental.