Autophagy in the physiology and pathology of the central nervous system

Abstract

Neurons are highly specialized postmitotic cells that depend on dynamic cellular processes for their proper function. These include among others, neuronal growth and maturation, axonal migration, synapse formation and elimination, all requiring continuous protein synthesis and degradation. Therefore quality-control processes in neurons are directly linked to their physiology. Autophagy is a tightly regulated cellular degradation pathway by which defective or superfluouscytosolic proteins, organelles and other cellular constituents are sequestered in autophagosomes and delivered to lysosomes for degradation. Here we present emerging evidence indicating that constitutive autophagic fluxin neurons has essential roles in key neuronal processes under physiological conditions. Moreover, we discuss how perturbations of the autophagic pathway may underlie diverse pathological phenotypes in neurons associated with neurodevelopmental and neurodegenerative diseases.