Alzheimer's disease: new approaches to drug discovery

被引:114
作者
Bolognesi, Maria L. [1 ]
Matera, Riccardo [1 ]
Minarini, Anna [1 ]
Rosini, Michela [1 ]
Melchiorre, Carlo [1 ]
机构
[1] Univ Bologna, Dept Pharmaceut Sci, I-40126 Bologna, Italy
关键词
BETA-SECRETASE; OXIDATIVE STRESS; MITOCHONDRIAL DYSFUNCTION; CHOLINERGIC HYPOTHESIS; AMYLOID-BETA; LADOSTIGIL; PROTEASE; TARGETS; ANTIOXIDANT; STRATEGIES;
D O I
10.1016/j.cbpa.2009.04.619
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:303 / 308
页数:6
相关论文
共 50 条
[1]   Neuroscience: THE PLAQUE PLAN [J].
Abbott, Alison .
NATURE, 2008, 456 (7219) :161-164
[2]   Mitochondrial medicine: Pharmacological targeting of mitochondria in disease [J].
Armstrong, J. S. .
BRITISH JOURNAL OF PHARMACOLOGY, 2007, 151 (08) :1154-1165
[3]   Oxidative stress: A dead end or a laboratory hypothesis? [J].
Azzi, Angelo .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 362 (02) :230-232
[4]   The Novel Cholinesterase-Monoamine Oxidase Inhibitor and Antioxidant, Ladostigil, Confers Neuroprotection in Neuroblastoma Cells and Aged Rats [J].
Bar-Am, Orit ;
Weinreb, Orly ;
Amit, Tamar ;
Youdim, Moussa B. H. .
JOURNAL OF MOLECULAR NEUROSCIENCE, 2009, 37 (02) :135-145
[5]  
BARRETT TD, 2004, DRUG DISCOV TODAY-TA, V3, P208
[6]   THE CHOLINERGIC HYPOTHESIS OF GERIATRIC MEMORY DYSFUNCTION [J].
BARTUS, RT ;
DEAN, RL ;
BEER, B ;
LIPPA, AS .
SCIENCE, 1982, 217 (4558) :408-417
[7]   Alzheimer's disease drug development in 2008 and beyond: Problems and opportunities [J].
Becker, Robert E. ;
Greig, Nigel H. .
CURRENT ALZHEIMER RESEARCH, 2008, 5 (04) :346-357
[8]   MTDL Design Strategy in the Context of Alzheimer's Disease: From Lipocrine to Memoquin and Beyond [J].
Bolognesi, M. L. ;
Rosini, M. ;
Andrisano, V. ;
Bartolini, M. ;
Minarini, A. ;
Tumiatti, V. ;
Melchiorre, C. .
CURRENT PHARMACEUTICAL DESIGN, 2009, 15 (06) :601-613
[9]   Memoquin: A Multi-Target-Directed Ligand as an Innovative Therapeutic Opportunity for Alzheimer's Disease [J].
Bolognesi, Maria Laura ;
Cavalli, Andrea ;
Melchiorre, Carlo .
NEUROTHERAPEUTICS, 2009, 6 (01) :152-162
[10]   Multi-target-directed ligands to combat neurodegenerative diseases [J].
Cavalli, Andrea ;
Bolognesi, Maria Laura ;
Minarini, Anna ;
Rosini, Michela ;
Tumiatti, Vincenzo ;
Recanatini, Maurizio ;
Melchiorre, Carlo .
JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (03) :347-372