On the search for multitarget inhibitors for BACE‐1 and other pharmacological targets of Alzheimer's Disease

  1. Domínguez Meijide, José Luís
Supervised by:
  1. María del Carmen Villaverde Cameron-Walker Director
  2. Fredy Sussman Co-director
  3. Ramón José Estévez Cabanas Co-director

Defence university: Universidade de Santiago de Compostela

Fecha de defensa: 11 July 2014

Committee:
  1. Ferran Sanz Carreras Chair
  2. María de los Angeles Castro Pérez Secretary
  3. Angelo Carotti Committee member
  4. Leonardo Pardo Carrasco Committee member
  5. Francisco Javier Sardina López Committee member
Department:
  1. Department of Organic chemistry

Type: Thesis

Abstract

Alzheimer disease (AD) is a devastating illness that affects populations worldwide, and for which an effective cure has yet to be found. We have studied in depth the effect of various factors like pH and ligand structure on the inhibition of BACE-1, one of the enzymes that produce the Aβ peptides, whose aggregation is a hallmark of this disease. The results of this study helped us to obtain drug leads that inhibit not only the aforementioned enzyme but some other AD therapeutic targets at the core of this illness. This study successfully identified several compounds with true multitarget potential against AD at the amyloidogenic and cholinergic levels.