Neurogenetik, Institut für Biologie, Freie Universität Berlin, 14195 Berlin, Germany.
NeuroCure, Cluster of Excellence, Charité Universitätsmedizin, 10117 Berlin, Germany.
Cells. 2019 Jan 9;8(1):34. doi: 10.3390/cells8010034.
Protein homeostasis (proteostasis) is crucial to the maintenance of neuronal integrity and function. As the contact sites between neurons, synapses rely heavily on precisely regulated protein-protein interactions to support synaptic transmission and plasticity processes. Autophagy is an effective degradative pathway that can digest cellular components and maintain cellular proteostasis. Perturbations of autophagy have been implicated in aging and neurodegeneration due to a failure to remove damaged proteins and defective organelles. Recent evidence has demonstrated that autophagosome formation is prominent at synaptic terminals and neuronal autophagy is regulated in a compartment-specific fashion. Moreover, synaptic components including synaptic proteins and vesicles, postsynaptic receptors and synaptic mitochondria are known to be degraded by autophagy, thereby contributing to the remodeling of synapses. Indeed, emerging studies indicate that modulation of autophagy may be required for different forms of synaptic plasticity and memory formation. In this review, I will discuss our current understanding of the important role of neuronal/synaptic autophagy in maintaining neuronal function by degrading synaptic components and try to propose a conceptual framework of how the degradation of synaptic components via autophagy might impact synaptic function and contribute to synaptic plasticity.
蛋白质动态平衡（蛋白质稳态）对于维持神经元的完整性和功能至关重要。作为神经元之间的接触点，突触严重依赖于精确调节的蛋白质-蛋白质相互作用来支持突触传递和可塑性过程。自噬是一种有效的降解途径，可以消化细胞成分并维持细胞蛋白质稳态。自噬的破坏与衰老和神经退行性变有关，因为它不能清除受损的蛋白质和有缺陷的细胞器。最近的证据表明，自噬体的形成在突触末端很明显，神经元自噬以特定区室的方式受到调节。此外，众所周知，突触成分包括突触蛋白和囊泡、突触后受体和突触线粒体通过自噬降解，从而有助于突触的重塑。事实上，新出现的研究表明，自噬的调节可能是不同形式的突触可塑性和记忆形成所必需的。在这篇综述中，我将讨论我们目前对神经元/突触自噬在通过降解突触成分来维持神经元功能方面的重要作用的理解，并试图提出一个概念框架，说明通过自噬降解突触成分如何影响突触功能并有助于突触可塑性。
