Abstract
Adult neurogenesis persists in the adult mammalian brain due to the existence of neural stem cell (NSC) reservoirs in defined niches, where they give rise to new neurons throughout life. Recent research has begun to address the implication of constitutive (basal) autophagy in the regulation of neurogenesis in the mature brain. This review summarizes the current knowledge on the role of autophagy-related genes in modulating adult NSCs, progenitor cells and their differentiation into neurons. The general function of autophagy in neurogenesis in several areas of the embryonic forebrain is also revisited. During development, basal autophagy regulates Wnt and Notch signaling and is mainly required for adequate neuronal differentiation. The available data in the adult indicate that the autophagy-lysosomal pathway regulates adult NSC maintenance, the activation of quiescent NSCs, the survival of the newly born neurons and the timing of their maturation. Future research is warranted to validate the results of these pioneering studies, refine the molecular mechanisms underlying the regulation of NSCs and newborn neurons by autophagy throughout the life-span of mammals and provide significance to the autophagic process in adult neurogenesis-dependent behavioral tasks, in physiological and pathological conditions. These lines of research may have important consequences for our understanding of stem cell dysfunction and neurogenic decline during healthy aging and neurodegeneration.
Highlights
Autophagy (“self-eating” in greek) is a highly conserved intracellular catabolic pathway that occurs in response to different forms of stress such as starvation, hypoxia, drugs, infection, growth factor deprivation and reactive oxygen species (ROS) accumulation
Autophagy is required for proper membrane turnover in axon terminals (Komatsu et al, 2007) and for neurogenesis, the production of new neurons from neural stem cells (NSCs)
We will provide a condensed review of the current knowledge about the physiological role of basal autophagy in neurogenesis, surveying the data available in embryonic development and the few studies conducted in adults
Summary
Autophagy (“self-eating” in greek) is a highly conserved intracellular catabolic pathway that occurs in response to different forms of stress such as starvation, hypoxia, drugs, infection, growth factor deprivation and ROS accumulation. The IM can be originated from other sources (Figure 1) and forms a cup-shaped structure termed the phagophore that recruits autophagy (Atg)-related proteins (Dikic and Elazar, 2018) This step can be modulated by the class III PI3K inhibitors 3-methyladenine (3-MA) and wortmannin (Wu et al, 2010). The fusion of the mature autophagosome’s outer membrane with the lysosome’s one leads to the degradation of the autophagosome’s inner membrane as well as its contents, generating building blocks recycled by the cell (Rodolfo et al, 2016) This final step can be modulated by bafilomycin A1, a disruptor of autophagosome-lysosome fusion and autophagolysosome acidification (Mauvezin and Neufeld, 2015).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
