Abstract
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.
Highlights
Neurons are connected at specialized contact sites called synapses
As a cellular quality control mechanism, plays an essential role in neuronal development, survival and homeostasis, as deregulation of autophagy has been implicated in neurodevelopmental disorders and neurodegeneration
What contents are engulfed by autophagosomes at synapses have been deciphered, including synaptic proteins and vesicles, mitochondria and postsynaptic receptors
Summary
Neurons are connected at specialized contact sites called synapses. These synaptic connections generate precise neural circuits and, form the fundamental basis for various neuronal activities and brain functions including sensory perception, motor action, sleep, memory and emotion. Shedding more light on this issue, their follow-up work firmly established a compartment-specific mechanism of constitutive autophagy in hippocampal neurons, hinting at a possibly conserved machinery underlying autophagosome maturation along the axon in different neuronal subtypes [28] It remains largely unknown how the spatial restriction of autophagosome biogenesis in distal axons is achieved. While autophagosomes are retrogradely transported along the axon to the soma, they are found to simultaneously carry brain-derived neurotrophic factor (BDNF)-TrkB signaling (Figure 1), in effect, mediating neuronal complexities and preventing neurodegeneration [29] Along these lines, the non-canonical role of autophagosomes as signaling organelles in stress and disease paradigms should be further investigated. The question arises as to what cargoes are degraded by autophagy at synaptic specializations
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