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Autophagy as a Homeostatic Mechanism in Response to Stress Conditions in the Central Nervous System

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Abstract

Autophagy is considered a major bulk degradation system that helps cells to counteract different intracellular and extracellular stress signals. Several protein complexes integrate multiple signals in order to activate autophagy, which sequesters damaged cellular components and carries them to lysosomes for degradation. This active mechanism is essential to maintain cell homeostasis and particularly in neurons to sustain their viability. Because of their polarized morphology, neurons face special challenges to recycle cellular components through autophagy in dendrites and distal regions of axons. Thus, autophagy is critical in the remodeling of pre- and post-synaptic constituents to sustain neuronal functionality. Under stress conditions, autophagy may play either a cytotoxic or a cytoprotective role. This discrepancy is partly due to the lack of a full characterization of the autophagic process and conclusive evidence to support whether basal autophagy is stimulated or impaired in a particular condition. Moreover, in many studies, only pharmacologic tools have been used to modulate autophagy. Throughout the present review, we go over the literature revealing autophagy induction in the nervous system under diverse stressful conditions, the signaling pathways involved, and its consequences for neuronal homeostasis and survival. We have focused on five particular stress conditions that alter neuronal homeostasis and can induce neuronal death including, starvation, oxidative stress, endoplasmic reticulum (ER) stress, proteotoxic stress, and aging.

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LM was supported by PAPIIT IN205416 grant from Universidad Nacional Autónoma de México and CGO from Estímulos a Investigaciones Médicas Miguel Alemán Valdés.

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  1. Cristian Gerónimo-Olvera

    Present address: Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile

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    Cristian Gerónimo-Olvera & Lourdes Massieu

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Gerónimo-Olvera, C., Massieu, L. Autophagy as a Homeostatic Mechanism in Response to Stress Conditions in the Central Nervous System. Mol Neurobiol 56, 6594–6608 (2019). https://doi.org/10.1007/s12035-019-1546-x

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