Alzheimer's disease: new approaches to drug discovery.
In this work, we review and comment upon the challenges and the 'quo vadis' in Alzheimer's disease drug discovery at the beginning of the new millennium. We emphasize recent approaches that, moving on from a target-centric approach, have produced innovative molecular probes or drug candidates. In particular, the discovery of endosome-targeted BACE1 inhibitors and mitochondria-targeted antioxidants represents a significant advance in Alzheimer's research and therapy. The case study of the development of rasagiline provides an excellent example to support the validity of the multitarget-designed ligand approach to the search for effective medicines for combating Alzheimer's disease.
Bolognesi
Maria L
ML
Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Matera
Riccardo
R
Minarini
Anna
A
Rosini
Michela
M
Melchiorre
Carlo
C
D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D016503:Drug Delivery Systems / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D007189:Indans / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000737:chemistry
C423264:(N-propargyl-(3R) aminoindan-5-yl)-ethyl methyl carbamate; D007189:Indans; D009943:Organophosphorus Compounds; D014451:Ubiquinone; C429014:mitoquinone; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human