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变废为宝:自噬在突触功能中的作用

Turning garbage into gold: Autophagy in synaptic function.

作者信息

Smith Erin Marie, Coughlan Maeve Louise, Maday Sandra

机构信息

Department of Neuroscience, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.

Department of Neuroscience, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Curr Opin Neurobiol. 2025 Feb;90:102937. doi: 10.1016/j.conb.2024.102937. Epub 2024 Dec 12.

Abstract

Trillions of synapses in the human brain enable thought and behavior. Synaptic connections must be established and maintained, while retaining dynamic flexibility to respond to experiences. These processes require active remodeling of the synapse to control the composition and integrity of proteins and organelles. Macroautophagy (hereafter, autophagy) provides a mechanism to edit and prune the synaptic proteome. Canonically, autophagy has been viewed as a homeostatic process, which eliminates aged and damaged proteins to maintain neuronal survival. However, accumulating evidence suggests that autophagy also degrades specific cargoes in response to neuronal activity to impact neuronal transmission, excitability, and synaptic plasticity. Here, we will discuss the diverse roles, regulation, and mechanisms of neuronal autophagy in synaptic function and contributions from glial autophagy in these processes.

摘要

人类大脑中的数万亿个突触促成了思维和行为。突触连接必须建立并维持,同时保持动态灵活性以应对各种经历。这些过程需要对突触进行积极重塑,以控制蛋白质和细胞器的组成与完整性。巨自噬(以下简称自噬)提供了一种编辑和修剪突触蛋白质组的机制。传统上,自噬被视为一种稳态过程,它清除老化和受损的蛋白质以维持神经元存活。然而,越来越多的证据表明,自噬也会响应神经元活动而降解特定的货物,从而影响神经元传递、兴奋性和突触可塑性。在这里,我们将讨论神经元自噬在突触功能中的多种作用、调节和机制,以及神经胶质自噬在这些过程中的贡献。

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