Amyloid-β-Heme Complex and Protein Tyrosine Nitration: Implications in Alzheimer's Desease

Abstract

Amyloid-β(Aβ) is the major component of amyloid plaques in Alzheimer's disease(AD).Aβ cascade hypothesis suggested that Aβ deposition in the brain substance is a critical step which eventually leads to Alzheimer's disease.A large number of studies have shown that soluble Aβ oligomers are more toxic than Aβ aggregates and may be associated with cognitive dysfunction.The metabolism of heme was found to be changed in the brain of AD patients.Meanwhile,Aβ was found to bind to heme,forming Aβ-heme complex,which might contributed to the alteration of heme homeostasis in AD.The binding of heme to Aβ can inhibit Aβ aggregation and also can dissociate the aggregated state of Aβ,indicating that the interaction of Aβ with heme can play an important role in AD.Interestingly,Aβ-heme complex was found to possess higher peroxidase activity than heme,and we found this complex was more effective than heme in catalyzing the nitration of proteins,which imply that Aβ-heme may be the molecular link between Aβ and the widespread protein nitration in AD.Moreover,Aβ binds to heme has been shown to change the selectivity of the heme catalyzed protein nitration.These studies would help to understand the physiological roles of Aβ-heme in vivo and may be helpful for AD prevention and treatment.