Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis

被引:85
作者
Dunkel, Petra [2 ]
Chai, Christina L. L. [3 ,4 ]
Sperlagh, Beata [5 ]
Huleatt, Paul B. [3 ]
Matyus, Peter [1 ,2 ]
机构
[1] Semmelweis Univ, Drug Discovery & Safety Ctr, H-1094 Budapest, Hungary
[2] Semmelweis Univ, Dept Organ Chem, H-1094 Budapest, Hungary
[3] Neuros, Inst Chem & Engn Sci, Singapore 138665, Singapore
[4] Natl Univ Singapore, Dept Pharm, Singapore 117543, Singapore
[5] Hungarian Acad Sci, Inst Expt Med, H-1083 Budapest, Hungary
基金
匈牙利科学研究基金会;
关键词
neurodegenerative; neuroprotective; Alzheimer's disease; Parkinson's disease; Huntington's disease; amyotrophic lateral sclerosis; multi-target-directed ligands; GAMMA-SECRETASE MODULATOR; RECEPTOR PARTIAL AGONIST; TARGET-DIRECTED LIGANDS; SITE ACETYLCHOLINESTERASE INHIBITORS; TRANSGENIC MOUSE MODEL; HISTAMINE H-3 RECEPTOR; NECROSIS-FACTOR-ALPHA; PYROGLUTAMATE-A-BETA; HEAT-SHOCK PROTEINS; AMYLOID-BETA;
D O I
10.1517/13543784.2012.703178
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: According to the definition of the Committee to Identify Neuroprotective Agents in Parkinson's Disease (CINAPS), "neuroprotection would be any intervention that favourably influences the disease process or underlying pathogenesis to produce enduring benefits for patients" [Meissner W, et al. Trends Pharmacol Sci 2004;25:249-253]. Preferably, neuroprotective agents should be used before or eventually during the prodromal phase of the diseases that could start decades before the appearance of symptoms. Although several symptomatic drugs are available, a disease-modifying agent is still elusive. Areas covered: The aim of the present review is to give an overview of neuroprotective agents being currently investigated for the treatment of AD, PD, HD and ALS in clinical phases. Expert opinion: Development of effective neuroprotective therapies resulting in clinically meaningful results is hampered by several factors in all research stages, both conceptual and methodological. Novel solutions might be offered by evaluation of new targets throughout clinical studies, therapies emerging from drug repositioning approaches, multi-target approaches and network pharmacology.
引用
收藏
页码:1267 / 1308
页数:42
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