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腺苷转运体与受体:视网膜功能及神经保护的关键要素

Adenosine transporters and receptors: key elements for retinal function and neuroprotection.

作者信息

Dos Santos-Rodrigues Alexandre, Pereira Mariana R, Brito Rafael, de Oliveira Nádia A, Paes-de-Carvalho Roberto

机构信息

Program of Neurosciences, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.

Program of Neurosciences, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.

出版信息

Vitam Horm. 2015;98:487-523. doi: 10.1016/bs.vh.2014.12.014. Epub 2015 Feb 27.

Abstract

Adenosine is an important neuroactive substance in the central nervous system, including in the retina where subclasses of adenosine receptors and transporters are expressed since early stages of development. Here, we review some evidence showing that adenosine plays important functions in the mature as well as in the developing tissue. Adenosine transporters are divided into equilibrative and concentrative, and the major transporter subtype present in the retina is the ENT1. This transporter is responsible for a bidirectional transport of adenosine and the uptake or release of this nucleoside appears to be regulated by different signaling pathways that are also controlled by activation of adenosine receptors. Adenosine receptors are also key players in retina physiology regulating a variety of functions in the mature and developing tissue. Regulation of excitatory neurotransmitter release and neuroprotection are the main functions played be adenosine in the mature tissue, while regulation of cell survival and neurogenesis are some of the functions played by adenosine in developing retina. Since adenosine is neuroprotective against excitotoxic and metabolic dysfunctions observed in neurological and ocular diseases, the search for adenosine-related drugs regulating adenosine transporters and receptors can be important for advancement of therapeutic strategies against these diseases.

摘要

腺苷是中枢神经系统中的一种重要神经活性物质,在视网膜中也存在,自发育早期起,视网膜中就表达腺苷受体和转运体的亚类。在此,我们回顾一些证据,这些证据表明腺苷在成熟组织以及发育中的组织中发挥着重要作用。腺苷转运体分为平衡型和浓缩型,视网膜中存在的主要转运体亚型是ENT1。这种转运体负责腺苷的双向运输,并且这种核苷的摄取或释放似乎受不同信号通路的调节,而这些信号通路也受腺苷受体激活的控制。腺苷受体也是视网膜生理学中的关键参与者,调节成熟组织和发育中组织的多种功能。调节兴奋性神经递质释放和神经保护是腺苷在成熟组织中发挥的主要功能,而调节细胞存活和神经发生是腺苷在发育中的视网膜中发挥的一些功能。由于腺苷对神经疾病和眼部疾病中观察到的兴奋性毒性和代谢功能障碍具有神经保护作用,因此寻找调节腺苷转运体和受体的腺苷相关药物对于推进针对这些疾病的治疗策略可能具有重要意义。

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