Determination of fibril disaggregation processes in Alzheimer's disease responsible Aß1-40 by means of solid state NMR

• Antragsteller: Dr. Juan Miguel López del Amo
• Fachliche Zuordnung: Pharmakologie
• Förderung: Förderung von 2008 bis 2012
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 60557221

Alzheimer s disease is the most common form of dementia, a group of disorders that impairs mental functioning. At the moment, Alzheimer s is progressive and irreversible. The progressive loss of cognitive function is accompanied by pathologic (disease-associated) changes in the brain. One of these is the formation of plaques in the space between nerve cells. The plaques are comprised of a brain protein called beta amyloid. The amyloid hypothesis“that the plaques are responsible for the pathology of Alzheimer s disease, is accepted by the majority of researchers. Recent investigations carried out by E. Wanker et al. from the Max Delbrueck Center for Molecular Medicine (MDC) have identified, by performing a screening of natural compounds, (-)-epigallocatechin-3-gallate (EGCG) and some related phenols as potent inhibitors of amyloid plaques in vivo. However, the interrelation between the fibril-inhibitor structure and the mechanism upon which these molecules destabilize the hydrogen bonding network stabilizing fibril structure remain a mystery. In the present project we propose a solid state NMR analysis of the hydrogen bonding and hydrophobic interactions in wild-type amyloid fibrils and in fibrils interacting with EGCG. This will give an important insight in the mechanisms upon which this molecule promotes fibril desegregation and provide useful information for future drug design.

• DFG-Verfahren: Forschungsstipendien
• Gastgeber: Professor Dr. Bernd Reif