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Two papers this week suggest that the process of protein degradation and clearance of cellular components may be more important in maintaining the health of the nervous system than was thought. Both groups show that inhibition of autophagy in mouse brain cells results in neurodegeneration and early death. Autophagy, the protein degradation and recycling of cellular components, is important for the normal growth and development of a cell. The finding that the continual clearance of cellular components is essential for maintaining neuronal health should open up new avenues of research into the nature of neurodegenerative diseases. One of two papers showing that loss of autophagy in the central nervous system of mice causes the accumulation of protein aggregates in inclusion bodies, neurodegeneration and premature death of the mice. This demonstrates that continuous clearance of cellular components is essential for proper housekeeping and vital to keep the neurons in tiptop shape. Autophagy is an intracellular bulk degradation process through which a portion of the cytoplasm is delivered to lysosomes to be degraded1,2,3,4. Although the primary role of autophagy in many organisms is in adaptation to starvation, autophagy is also thought to be important for normal turnover of cytoplasmic contents, particularly in quiescent cells such as neurons. Autophagy may have a protective role against the development of a number of neurodegenerative diseases5,6,7,8. Here we report that loss of autophagy causes neurodegeneration even in the absence of any disease-associated mutant proteins. Mice deficient for Atg5 (autophagy-related 5) specifically in neural cells develop progressive deficits in motor function that are accompanied by the accumulation of cytoplasmic inclusion bodies in neurons. In Atg5-/- cells, diffuse, abnormal intracellular proteins accumulate, and then form aggregates and inclusions. These results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration.

Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. Despite its simplicity, recent progress has demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles, which are sometimes complex. Autophagy consists of several sequential steps—sequestration, transport to lysosomes, degradation, and utilization of degradation products—and each step may exert different function. In this review, the process of autophagy is summarized, and the role of autophagy is discussed in a process-based manner.