Neuronal Autophagy and Neurodevelopmental Disorders (original) (raw)

2013, Experimental Neurobiology

Autophagy, which is a highly conserved pathway from yeast to mammals, is a major catabolic process that delivers cytosolic components to lysosomes for degradation. It is considered to be important for cellular homeostasis, especially under nutrientdeficient or stress conditions, by degrading cytosolic materials in order to either supply the components required for alternate energy metabolism pathways or remove toxic components for cell survival. However, a growing body of evidence has suggested that autophagy is constitutively activated during normal nutrient conditions in a cell-type specific manner. Autophagy has been implicated in various cellular processes such as protein and organelle quality control, development and differentiation, ageing, and immunity. Therefore, alteration of autophagy is associated with several cellular pathologies and diseases, including tumor formation, infectious diseases, liver diseases, myopathy, diabetes, and several neurodegenerative diseases [1, 2]. Autophagy can be generally classified as microautophagy, chaperone-mediated (CMA), or macroautophagy [2-4]. Microautophagy delivers the cytoplasmic contents by invagination of the lysosomal membrane into its lumen. CMA involves the selective sequestration of proteins with a KFERQ-like motif into lysosomes via chaperones Hsc70 and LAMP-2A (Lysosomal-Associated Membrane Protein-2A) complex. Macroautophagy (referred to as autophagy) is the well-characterized form of autophagy that involves the sequestration of cytosolic components into lysosomes in a non-selective manner. Although autophagy is mostly a non