Protein homeostasis and degradation in quiescent neural stem cells

Tissue stem cells are maintained in the adult body throughout life and are crucial for tissue homeostasis as they supply newly functional cells. Quiescence is a reversible arrest in the G0/G1 phase of the cell cycle and a strategy to maintain the quality of tissue stem cells. Quiescence maintains stem cells in a self-renewable and differentiable state for a prolonged period by suppressing energy consumption and cell damage and depletion. Most adult neural stem cells in the brain maintain the quiescent state and produce neurons and glial cells through differentiation after activating from the quiescent state to the proliferating state. In this process, proteostasis, including proteolysis, is essential to transition between the quiescent and proliferating states associated with proteome remodeling. Recent reports have demonstrated that quiescent and proliferating neural stem cells have different expression patterns and roles as proteostatic molecules and are affected by age, indicating differing processes for protein homeostasis in these two states in the brain. This review discusses the multiple regulatory stages from protein synthesis (protein birth) to proteolysis (protein death) in quiescent neural stem cells.