Presynaptic nerve terminals are highly specialized vesicle-trafficking machines. Neurotransmitter release from these terminals is sustained by constant local recycling of synaptic vesicles independent from the neuronal cell body. This independence places significant constraints on maintenance of synaptic protein complexes and scaffolds. Key events during the synaptic vesicle cycle-such as exocytosis and endocytosis-require formation and disassembly of protein complexes. This extremely dynamic environment poses unique challenges for proteostasis at synaptic terminals. Therefore, it is not surprising that subtle alterations in synaptic vesicle cycle-associated proteins directly or indirectly contribute to pathophysiology seen in several neurologic and psychiatric diseases. In contrast to the increasing number of examples in which presynaptic dysfunction causes neurologic symptoms or cognitive deficits associated with multiple brain disorders, synaptic vesicle-recycling machinery remains an underexplored drug target. In addition, irrespective of the involvement of presynaptic function in the disease process, presynaptic machinery may also prove to be a viable therapeutic target because subtle alterations in the neurotransmitter release may counter disease mechanisms, correct, or compensate for synaptic communication deficits without the need to interfere with postsynaptic receptor signaling. In this article, we will overview critical properties of presynaptic release machinery to help elucidate novel presynaptic avenues for the development of therapeutic strategies against neurologic and neuropsychiatric disorders.

中文翻译：

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突触小泡回收机械组件作为潜在的治疗目标。

突触前神经末梢是高度专门的囊泡贩运机器。从这些末端释放的神经递质通过独立于神经元细胞体的突触小泡的持续局部再循环而得以维持。这种独立性对突触蛋白复合物和支架的维持提出了重大限制。突触小泡周期中的关键事件（如胞吐作用和胞吞作用）需要蛋白质复合物的形成和分解。这种极其动态的环境对突触末端的蛋白稳态提出了独特的挑战。因此，毫不奇怪的是，突触囊泡周期相关蛋白的细微变化直接或间接地导致了几种神经系统疾病和精神疾病中所观察到的病理生理。与突触前功能障碍导致与多种脑部疾病相关的神经系统症状或认知缺陷的例子数量不断增加相反，突触小泡回收机制仍然是药物开发的目标。此外，无论突触前功能是否参与疾病过程，突触前机制也可能被证明是可行的治疗目标，因为神经递质释放的细微变化可抵消疾病机制，纠正或补偿突触通讯缺陷，而无需干扰突触后受体信号。在本文中，我们将概述突触前释放机制的关键特性，以帮助阐明开发针对神经系统疾病和神经精神疾病的治疗策略的新型突触前途径。