Final Report Summary - ABETAALPHASYNTAU (Insight into the synergistic interactions between Aβ amyloid, α-synuclein and Tau) The projects in the proposal are focused on a question that in the last tens years is raised: why patients with Alzheimer's disease have the risk to develop Parkinson's disease and vis-a-vis. We extended this research to the question of why patients with type 2 diabetes have the risk to develop Alzheimer's disease and/or Parkinson's disease in later life? This question also raised in the last 20 years.To provide insight into the link between these diseases, the poropsal suggested that there are interactions between amyloids that are related to these diseases. This suggestion has been proven by in vitro, in vivo and clinical studies, but still there was a lck to understand the mechanisms of the interactions between these amyloids, particularly at the atomic resolution.This proposal was aimed to provide insight into the interactions between various type of amyloid oligomers, which are the toxic species in these disease. We succeded to illustrates the interactions between various amyloids and provided insigh into the link beween diseases. We published 10 peer-reviewed articles on the projects performed for this proposal (see publications).The main highlights of the results:1. We are the first in the world that proposed at the atomic resolution the structure of NAC oligomers: The NAC domain plays important role in the aggregation of alpha-synuclein (AS) in Parkinson's disease. Yet, it is still unkown how AS proteins are self-assembled to form the toxic oligomers. We focused on the NAC domain and illustrated the mechanism through which the NAC peptides are self-assembled into oligomers.2. We are the first in the world that showed the interactions between various types of amyloids at the atomic resolution to form oligomers. While the current experimental tools cannot provide any information on these interactions at the atomic resolution, we have the computational modeling tools to tackle this issue. We found polymorhic states and various type of interactions between amyloid oligomers. We wrote several papers on these findings and will submit soon more papers.The impact of the research project of this proposal is fairly high, as it is already was proven by the citation of our papers. It has a great interest in the amyloid community and initiate other groups to work on this important global diseases in the world.The acheivements of this work allow us to understand the mechanisms that explain how patients with tpye 2 diabetes have the risk to develop Alzheimer's disease or Parkinson's disease. We currently can design an inhibitor to prevent that patients with type 2 diabetes to develop Alzheimer's disease or Parkinson's disease.
