Novel Therapeutic Modalities to Address Nondrugable Protein Interaction Targets

被引：30
作者：
De Souza, Errol B. [1 ]
Cload, Sharon T. [1 ]
Pendergrast, Patrick Shannon [1 ]
Sah, Dinah W. Y. [2 ]
机构：
[1] Archemix Corp, Cambridge, MA 02142 USA
[2] Alnylam Pharmaceut, Cambridge, MA USA
来源：
NEUROPSYCHOPHARMACOLOGY | 2009年 / 34卷 / 01期
关键词：
antibodies; aptamers; antisense; protein-protein interaction; siRNA; target validation; SMALL INTERFERING RNA; C-14-LABELED PHOSPHOROTHIOATE OLIGONUCLEOTIDE; INTERLEUKIN-12/23; MONOCLONAL-ANTIBODY; RESTORES DYSTROPHIN EXPRESSION; AMYLOID-BETA-PEPTIDE; NERVE GROWTH-FACTOR; MOUSE MODEL; A-BETA; ALZHEIMERS-DISEASE; TRANSGENIC MICE;
D O I：
10.1038/npp.2008.115
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Small molecule drugs are relatively effective in working on 'drugable' targets such as GPCRs, ion channels, kinases, proteases, etc but ineffective at blocking protein-protein interactions that represent an emerging class of 'nondrugable' central nervous system (CNS) targets. This article provides an overview of novel therapeutic modalities such as biologics (in particular antibodies) and emerging oligonucleotide therapeutics such as antisense, small-interfering RNA, and aptamers. Their key properties, overall strengths and limitations, and their utility as tools for target validation are presented. In addition, issues with regard to CNS targets as it relates to the blood-brain barrier penetration are discussed. Finally, examples of their application as therapeutics for the treatment of pain and some neurological disorders such as Alzheimer's disease, multiple sclerosis, Huntington's disease, and Parkinson's disease are provided.
引用
收藏
页码：142 / 158
页数：17
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