Functional dissection of astrocyte-secreted proteins: Implications in brain health and diseases

Astrocytes, which are homeostatic cells of the central nervous system (CNS), display remarkable heterogeneity in their morphology and function. Besides their physical and metabolic support to neurons, astrocytes modulate the blood-brain barrier, regulate CNS synaptogenesis, guide axon pathfinding, maintain brain homeostasis, affect neuronal development and plasticity, and contribute to diverse neuropathologies via secreted proteins. The identification of astrocytic proteome and secretome profiles has provided new insights into the maintenance of neuronal health and survival, the pathogenesis of brain injury, and neurodegeneration. Recent advances in proteomics research have provided an excellent catalog of astrocyte-secreted proteins. This review categorizes astrocyte-secreted proteins and discusses evidence that astrocytes play a crucial role in neuronal activity and brain function. An in-depth understanding of astrocyte-secreted proteins and their pathways is pivotal for the development of novel strategies for restoring brain homeostasis, limiting brain injury/inflammation, counteracting neurodegeneration, and obtaining functional recovery.