Free Heme and Amyloid beta: A Fatal Liaison in Alzheimer's Disease
What is it about?
In this study we investigated a possible role of complexes formed from free heme and Amyloid beta at Alzheimer's disease (AD). These complexes exhibit peroxidase activity after activation by hydrogen peroxide. This enzymatic activity may contribute to the oxidative stress observed at AD. Moreover, in this study we showed an effect of the named enzymatic activity on the formation of Amyloid beta fibrils as different fibrillation kinetics and altered fibril morphology were observed. Most interestingly, both the complex formation between free heme and Amyloid beta as well as the subsequent peroxidase activity depends on the human-specific sequence of Amyloid beta.
Why is it important?
In this study for the first time systematic mutational studies were performed on the N-terminal part of Amyloid beta to clarify the role of the human-specific amino acids R5, Y10 and H13 for the formation of complexes with free heme and the subsequent peroxidase activity.