Dopamine receptor downregulation: an alternative strategy for schizophrenia treatment
Dopamine receptor downregulation: an alternative strategy for schizophrenia treatment
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DOI：
10.1016/j.mehy.2004.04.012
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发表时间：
2004-01-01
影响因子：
4.7
通讯作者：
Tsai, SJ
中科院分区：
文献类型：
--
作者：
Tsai, SJ
精神分裂症是一种常见且具有毁灭性的疾病。精神分裂症的病因仍然未知，“多巴胺假说”的最简单表述认为精神分裂症是由多巴胺能过度活跃引起的。根据精神分裂症多巴胺能过度活跃的假设，阻断多巴胺 D2 受体 (DRD2) 的抗精神病药物和其他减少多巴胺 (DA) 传递的方法已被用于治疗精神分裂症。我认为多巴胺受体（DR）下调可能是一种替代策略，可以缓解与精神分裂症发病机制有关的多巴胺能过度活动。激动剂诱导的受体下调包括受体蛋白水解、受体基因转录的调节和RNA稳定性的影响。这些过程导致现有受体的减少和受体合成的减少。这一假设可以解释 DA 激动剂或部分激动剂（如阿立哌唑）的抗精神病机制。有人建议开发增加 DR 下调的药物可能是精神分裂症治疗的替代策略。 (C) 2004 Elsevier Ltd. 保留所有权利。
Schizophrenia is a common and devastating illness. The cause of schizophrenia is still unknown and the simplest formulation of the "Dopamine hypothesis" posits that schizophrenia results from dopaminergic hyperactivity. Under the hypothesis of dopaminergic hyperactivity in schizophrenia, antipsychotics blocking the dopamine D2 receptor (DRD2) and other approaches to reduce dopamine (DA) transmission have been used to treat schizophrenia. I propose that dopamine receptor (DR) downregulation could be an alternative strategy to compromise dopaminergic overactivity implicated in the pathogenesis of schizophrenia. Agonist-induced receptor downregulation includes receptor proteolysis, modulation of receptor gene transcription and affecting of RNA stability. These processes cause a decrease of existing receptors and reduction of receptor synthesis. This hypothesis could explain the antipsychotic mechanisms of DA agonists or partial agonists, like aripiprazole. It is suggested that the development of agents that increase DR downregulation could be an alternative strategy for schizophrenia treatment. (C) 2004 Elsevier Ltd. All rights reserved.