Interaction of amyloid β peptides with redox active heme cofactor: Relevance to Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder that has generally been associated with the accumulation of amyloid beta (A beta) peptides and the formation of partially reduced oxygen species (PROS) catalyzed by redox active transition metal bound A beta active sites in the brain. Heme binding to these A beta peptides has opened up a new direction in the field of AD. This review illustrates the role of heme in AD and discusses the nature of active site environment of the heme-A beta complexes. The peroxidase activity of the heme-A beta complexes has been discussed, highlighting the significance of 2nd sphere residues. The A beta peptides can simultaneously bind heme and Cu retaining the electronic, chemical and electrochemical properties of the individual metal sites. The heme-A beta, Cu-A beta and both heme and Cu bound A beta (heme-Cu-A beta) complexes exhibit harmful PROS generating properties and the redox active Tyr(10) residue has been demonstrated to play a significant role in PROS formation. Finally some possible therapeutics and their limitations relevant to AD are discussed. (C) 2012 Elsevier B.V. All rights reserved.