中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (7): 1170-1174.doi: 10.4103/1673-5374.235021

• 综述:退行性病与再生 • 上一篇    下一篇

淀粉样蛋白β和游离血红素:对阿尔茨海默病发病机制的新的见解

  

  • 收稿日期:2018-05-17 出版日期:2018-07-15 发布日期:2018-07-15

Amyloid β and free heme: bloody new insights into the pathogenesis of Alzheimer’s disease

Jörg Flemmig1, Marcel Zámocký2, 3, A Alia1, 4   

  1. 1 Institute for Medical Physics and Biophysics, Medical Faculty, Leipzig University, Leipzig, Germany
    2 Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava, Slovakia
    3 Institute of Chemical, Environmental and Biological Engineering, Faculty of Technical Chemistry, Vienna University of Technology, Vienna, Austria
    4 Leiden Institute of Chemistry, Faculty of Science, Leiden University, Leiden, The Netherlands
  • Received:2018-05-17 Online:2018-07-15 Published:2018-07-15
  • Contact: Jorg Flemmig, Ph.D., joerg.flemmig@medizin.uni-leipzig.de
  • Supported by:

    The work was supported by the Alzheimer Forschung Initiative e.V. (AFI 13810).

摘要:

orcid:0000-0001-5872-3373(Jörg Flemmig)

Abstract:

The cerebral formation of Amyloid β (Aβ) is a critical pathological feature of Alzheimer’s disease (AD). An accumulation of this peptide as senile plaques (SP) was already reported by Alois Alzheimer, the discoverer of the disease. Yet the exact contribution of Aβ to AD development remains elusive. Moreover, while extensive cerebral Aβ formation leads to fibril formation in many species, AD-like symptoms apparently depend on the highly conserved N-terminal residues R5, Y10 and H13. The amino acids were also shown to lead to the formation of Aβ-heme complexes, which exhibit peroxidase activity in the presence of H2O2. Taking together these observations we propose that the formation and enzymatic activity of the named complexes may represent an essential aspect of AD pathology. Furthermore, Aβ is also known to lead to cerebral micro-vessel destruction (CAA) as well as to hemolytic events. Thus we suggest that the Aβ-derived cerebral accumulation of blood-derived free heme represents a likely precondition for the subsequent formation of Aβ-heme complexes.

Key words: Alzheimer’s disease, amyloid &beta, sequence, amyloid β-heme complexes, peroxidase activity, dityrosine formation, cerebral amyloid angiopathy, hemolysis