Neuronal Autophagy in Synaptic Functions and Psychiatric Disorders

Abstract

Homeostatic maintenance of physiological functions is fundamental to organismal well-being. Disruption or imbalance in homeostasis results in functional disturbances at molecular, cellular, and tissue levels, leading to manifestation as physical and mental illnesses. Homeostatic imbalance is caused by a range of pathophysiological mechanisms, including disrupted reduction-oxidation reactions, inflammatory responses, metabolic disturbances, or failure in quality control of cellular proteins and organelles. However, the roles for the protein/organelle quality control in the regulation of behaviors, in particular of cognitive processes, had not been well documented, until recent reports finally supported this concept. The frontline studies in neuroscience have revealed that synaptic components (e.g., synaptic proteins, organelles, neurotransmitters and their receptors) are selectively degraded by autophagy, a cellular recycling machinery implicated in surveillance and quality control of proteins and organelles responsible for the maintenance of cellular homeostasis. Apart from the canonical role of autophagy in supporting cell viability, synaptic autophagy appears to regulate synapse remodeling and plasticity. Consistently, emerging evidence suggests novel roles of autophagy in memory encoding, information processing, or cognitive functions. In this review, we overview recent progress in understanding the roles of neuronal autophagy in homeostatic maintenance of synaptic functions, with particular focus on how disruptions in these processes may contribute to the pathophysiology of psychiatric disorders.

Keywords: Aggregate; Autophagy; Cognition; Homeostasis; Psychiatric disorders; Synapse.