Targeting ligand-operated chaperone sigma-1 receptors in the treatment of neuropsychiatric disorders.
Targeting ligand-operated chaperone sigma-1 receptors in the treatment of neuropsychiatric disorders.
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靶向配体的伴侣伴侣Sigma-1受体在神经精神疾病的治疗中。
DOI：
10.1517/14728222.2011.560837
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发表时间：
2011-05
影响因子：
5.8
通讯作者：
Su TP
中科院分区：
文献类型：
--
作者：
Hayashi T;Tsai SY;Mori T;Fujimoto M;Su TP
目前用于治疗精神或神经退行性疾病的常规治疗药物有一定的使用局限性。精神治疗药物，如典型和非典型抗精神病药、三环抗抑郁药和选择性单胺再摄取抑制剂，旨在使单胺能系统的高或低神经传递正常化。尽管它们对精神病患者的预后有很大的贡献，但这些药物往往会产生严重的副作用，需要长期治疗才能促进症状的改善。此外，可用于治疗神经退行性疾病的药物严重有限。这篇综述讨论了最近的证据已经阐明了sigma-1受体配体，这可能是一类新的抗抑郁药或神经保护剂。Sigma-1受体是一种新型的配体操作分子伴侣，调节多种信号转导、内质网应激、细胞氧化还原、细胞存活和突触发生。选择性sigma-1受体配体在临床前研究中发挥快速的抗抑郁样，抗焦虑，抗伤害和强大的神经保护作用。最近的研究表明，活性氧可能在sigma- 1rs下游的信号整合器中起着至关重要的作用。在过去的十年中，sigma受体研究的重大进展已经开始阐明sigma-1受体上游和下游的细胞内信号级联。sigma-1受体伴侣的新型配体操作特性可能使各种干预成为可能，通过这些干预，压力相关的细胞系统可以得到药理学控制。
Current conventional therapeutic drugs for the treatment of psychiatric or neurodegenerative disorders have certain limitations of use. Psychotherapeutic drugs such as typical and atypical antipsychotics, tricyclic antidepressants, and selective monoamine reuptake inhibitors, aim to normalize the hyper- or hypo-neurotransmission of monoaminergic systems. Despite their great contribution to the outcomes of psychiatric patients, these agents often exert severe side effects and require chronic treatments to promote amelioration of symptoms. Furthermore, drugs available for the treatment of neurodegenerative disorders are severely limited. This review discusses recent evidence that has shed light on sigma-1 receptor ligands, which may serve as a new class of antidepressants or neuroprotective agents. Sigma-1 receptors are novel ligand-operated molecular chaperones regulating a variety of signal transduction, ER stress, cellular redox, cellular survival, and synaptogenesis. Selective sigma-1 receptor ligands exert rapid antidepressant-like, anxiolytic, antinociceptive and robust neuroprotective actions in preclinical studies. The review also looks at recent studies which suggest that reactive oxygen species might play a crucial role as signal integrators at the downstream of Sig-1Rs The significant advances in sigma receptor research in the last decade have begun to elucidate the intracellular signal cascades upstream and downstream of sigma-1 receptors. The novel ligand-operated properties of the sigma-1 receptor chaperone may enable a variety of interventions by which stress-related cellular systems are pharmacologically controlled.
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DOI：
10.1126/science.1166127
发表时间：
2009-02-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fontanilla D;Johannessen M;Hajipour AR;Cozzi NV;Jackson MB;Ruoho AE
通讯作者：
Ruoho AE
影响因子：
13.5
作者：
Fishback, James A.;Robson, Matthew J.;Xu, Yan-Tong;Matsumoto, Rae R.
通讯作者：
Matsumoto, Rae R.
DOI：
10.1073/pnas.0402890101
发表时间：
2004-10-12
影响因子：
11.1
作者：
Hayashi, T;Su, TP
通讯作者：
Su, TP
影响因子：
2.3
作者：
GOLDSTEIN, SR;MATSUMOTO, RR;WALKER, JM
通讯作者：
WALKER, JM
影响因子：
10.6
作者：
Bloch, M;Schmidt, PJ;Rubinow, DR
通讯作者：
Rubinow, DR