The cellular pathways of neuronal autophagy and their implication in neurodegenerative diseases

Autophagy is a tightly regulated cell self-eating process. It has been shown to be associated with various neuropathological conditions and therefore, traditionally known as a stress-induced process. Recent studies, however, reveal that autophagy is constitutively active in healthy neurons. Neurons are highly specialized, post-mitotic cells that are typically composed of a soma (cell body), a dendritic tree, and an axon. Despite the vast growth of our current knowledge of autophagy, the detailed process in such a highly differentiated cell type remains elusive. Current evidence strongly suggests that autophagy is uniquely regulated in neurons and is also highly adapted to local physiology in the axons. In addition, the molecular mechanism for basal autophagy in neurons may be significantly divergent from "classical" induced autophagy. A considerable number of studies have increasingly shown an important role for autophagy in neurodegenerative diseases and have explored autophagy as a potential drug target. Thus, understanding the neuronal autophagy process will ultimately aid in drug target identification and rational design of drug screening to combat neurodegenerative diseases. (C) 2009 Elsevier B.V. All rights reserved.