Adenosine hypothesis of schizophrenia--opportunities for pharmacotherapy.
Adenosine hypothesis of schizophrenia--opportunities for pharmacotherapy.
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DOI：
10.1016/j.neuropharm.2011.01.048
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发表时间：
2012-03
影响因子：
4.7
通讯作者：
Yee, Benjamin K.
中科院分区：
文献类型：
--
作者：
Boison, Detlev;Singer, Philipp;Shen, Hai-Ying;Feldon, Joram;Yee, Benjamin K.
基于多巴胺假说的精神分裂症的药物治疗对于该疾病的阴性和认知症状仍然不令人满意。增强N-甲基-d-天冬氨酸受体（NMDAR）功能有望缓解此类持续性症状，但成功开发新型临床有效化合物仍具有挑战性。腺苷是一种稳态生物能量网络调节剂，能够在不同水平（受体依赖性途径、生物化学、生物能量学和表观遗传学）协同影响复杂网络。通过影响大脑多巴胺和谷氨酸的活动，它代表了一个有前途的候选人，恢复这些神经递质系统的功能不平衡，相信是精神分裂症症状的起源，以及恢复生物能量的稳态。精神分裂症的腺苷假说进一步表明，腺苷能功能障碍可能通过不同的机制导致精神分裂症特征性的多种神经递质功能障碍的出现。由于腺苷在早期脑发育和脑免疫反应调节中的重要性，它也与精神分裂症的病因学直接相关。在这里，我们提供了一个概述的理由和证据，支持治疗潜力的多个腺苷能靶点，包括高亲和力腺苷受体（A1 R和A2 AR），和调节酶腺苷激酶（ADK）。关键的初步临床数据和临床前研究结果进行审查。
Pharmacotherapy of schizophrenia based on the dopamine hypothesis remains unsatisfactory for the negative and cognitive symptoms of the disease. Enhancing N-methyl-d-aspartate receptors (NMDAR) function is expected to alleviate such persistent symptoms, but successful development of novel clinically effective compounds remains challenging. Adenosine is a homeostatic bioenergetic network modulator that is able to affect complex networks synergistically at different levels (receptor dependent pathways, biochemistry, bioenergetics, and epigenetics). By affecting brain dopamine and glutamate activities it represents a promising candidate for restoring the functional imbalance in these neurotransmitter systems believed to underlie the genesis of schizophrenia symptoms, as well as restoring homeostasis of bioenergetics. Suggestion of an adenosine hypothesis of schizophrenia further posits that adenosinergic dysfunction might contribute to the emergence of multiple neurotransmitter dysfunctionscharacteristic of schizophrenia via diverse mechanisms. Given the importance of adenosine in early brain development and regulation of brain immune response, it also bears direct relevance to the aetiology of schizophrenia. Here, we provide an overview of the rationale and evidence in support of the therapeutic potential of multiple adenosinergic targets, including the high-affinity adenosine receptors (A1R and A2AR), and the regulatory enzyme adenosine kinase (ADK). Key preliminary clinical data and preclinical findings are reviewed.
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影响因子：
12.4
作者：
Boison, D.;Chen, J-F;Fredholm, B. B.
通讯作者：
Fredholm, B. B.
DOI：
10.1590/s0100-879x2002001000013
发表时间：
2002-10-01
影响因子：
2.3
作者：
Angelucci, M.E.M.;Cesário, C.;Cunha, C. Da
通讯作者：
Cunha, C. Da
DOI：
10.1073/pnas.97.14.8104
发表时间：
2000-07-05
影响因子：
11.1
作者：
Abi-Dargham, A;Rodenhiser, J;Laruelle, M
通讯作者：
Laruelle, M
影响因子：
4.7
作者：
Boeck, CR;Kroth, EH;Vendite, D
通讯作者：
Vendite, D
影响因子：
--
作者：
Boison, Detlev
通讯作者：
Boison, Detlev