Synaptic Vesicle Glycoprotein 2A: Features and Functions.
Synaptic Vesicle Glycoprotein 2A: Features and Functions.
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DOI：
10.3389/fnins.2022.864514
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发表时间：
2022
影响因子：
4.3
通讯作者：
Landau, Anne M.
中科院分区：
文献类型：
--
作者：
Rossi, Rachele;Arjmand, Shokouh;Baerentzen, Simone Larsen;Gjedde, Albert;Landau, Anne M.
关键词：
近年来，通过快速开发新靶点的特异性放射性配体，神经影像领域取得了巨大的进步。在这些靶标中，突触小泡糖蛋白 2A (SV2A) 是突触小泡的跨膜蛋白，存在于所有突触末端，与神经递质含量无关。它涉及神经元的关键功能，重点是神经递质释放的调节。大脑灰质区域的普遍表达是其作为突触密度标记的候选资格的基础。随着选择性结合 SV2A 的抗癫痫药物左乙拉西坦结构衍生的分子的开发，已经合成了几种放射性标记标记物，以便通过正电子发射断层扫描 (PET) 研究 SV2A 的分布。这些放射性配体允许评估 SV2A 分布的体内变化，这被认为是生理和病理条件下突触密度的潜在测量。使用 SV2A 作为突触密度的生物标志物提出了重要的问题。尽管过去几十年进行了大量研究，但 SV2A 的生物学功能和表达特性仍然知之甚少。 SV2A 的一些功能已被声称，但尚未完全阐明。虽然 SV2A 的表达无处不在，但在某些大脑结构中观察到 SV2A 与 Y 氨基丁酸 (GABA) 能突触而非谷氨酸能突触之间的关联更强。另一个问题是 SV2A 与其示踪剂之间的相互作用尚不清楚，这反映出需要澄清神经影像工具真正检测到的内容。在这里，我们总结了 SV2A 蛋白的当前知识，并讨论了 SV2A 生物学和生理学的不确定方面。由于 SV2A 表达无处不在，但在特定情况下可能与某种类型的神经传递密切相关，因此对该蛋白质的更广泛了解将极大地促进神经影像结果的分析和解释，因为不仅可以评估蛋白质水平的增加或减少，还可以评估所涉及的神经传递类型。
In recent years, the field of neuroimaging dramatically moved forward by means of the expeditious development of specific radioligands of novel targets. Among these targets, the synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane protein of synaptic vesicles, present in all synaptic terminals, irrespective of neurotransmitter content. It is involved in key functions of neurons, focused on the regulation of neurotransmitter release. The ubiquitous expression in gray matter regions of the brain is the basis of its candidacy as a marker of synaptic density. Following the development of molecules derived from the structure of the anti-epileptic drug levetiracetam, which selectively binds to SV2A, several radiolabeled markers have been synthetized to allow the study of SV2A distribution with positron emission tomography (PET). These radioligands permit the evaluation of in vivo changes of SV2A distribution held to be a potential measure of synaptic density in physiological and pathological conditions. The use of SV2A as a biomarker of synaptic density raises important questions. Despite numerous studies over the last decades, the biological function and the expressional properties of SV2A remain poorly understood. Some functions of SV2A were claimed, but have not been fully elucidated. While the expression of SV2A is ubiquitous, stronger associations between SV2A and Υ amino butyric acid (GABA)-ergic rather than glutamatergic synapses were observed in some brain structures. A further issue is the unclear interaction between SV2A and its tracers, which reflects a need to clarify what really is detected with neuroimaging tools. Here, we summarize the current knowledge of the SV2A protein and we discuss uncertain aspects of SV2A biology and physiology. As SV2A expression is ubiquitous, but likely more strongly related to a certain type of neurotransmission in particular circumstances, a more extensive knowledge of the protein would greatly facilitate the analysis and interpretation of neuroimaging results by allowing the evaluation not only of an increase or decrease of the protein level, but also of the type of neurotransmission involved.
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DOI：
10.1016/j.trci.2017.08.004
发表时间：
2017-11-01
期刊：
Alzheimer's & dementia (New York, N. Y.)
影响因子：
--
作者：
Bahri, Mohamed Ali;Plenevaux, Alain;Salmon, Eric
通讯作者：
Salmon, Eric
影响因子：
56.9
作者：
BAJJALIEH, SM;PETERSON, K;SCHELLER, RH
通讯作者：
SCHELLER, RH
影响因子：
3.2
作者：
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通讯作者：
Carson, Richard E.
影响因子：
3.1
作者：
Constantinescu, Cristian C.;Tresse, Cedric;Barret, Olivier
通讯作者：
Barret, Olivier
影响因子：
29
作者：
Chen, Ming-Kai;Mecca, Adam P.;van Dyck, Christopher H.
通讯作者：
van Dyck, Christopher H.