Suppression of basal autophagy in neural cells

causes neurodegenerative disease in mice

Nature 441: 885-889 (2006)

Speaker : Chia-Min Kao                       Date: 10.04.2006

Commentator : Dr. Yu-Min Kuo                 Time: 14:00~15:00

Abstract:

Autophagy is an evolutionarily conserved mechanism which happens in all eukaryotic cells. When cells sense starvation, autophagy will turn on. Cellular organelles or components will be sequestered in a double-membrane structure, autophagosome, before fusion with lysosome to form autophagolysosome. The cellular components within autophagolysosome will be degraded into nutrients, so starvated cells can survive. Besides starvation, autophagy also plays an important role in maintaining cell health. Previous studies showed that constitutive and low level of autophagy can prevent the development of several neurodegenerative diseases by clearing intracellular metabolic materials. Because mice without Atg5 (autophagy-related 5), an important component of autophagosome, will die soon after birth^1,2, the authors generated another autophagy deficient mice to investigate the relationship between autophagy and neurodegenerative diseases using Cre-loxP inducible system. Only the Atg5 of neurons in these mice were deleted. They found that the Atg5 deficient mice had behavioral abnormalities, neurodegeneration, and ubiquitin-positive accumulation in neurons. These results showed that continual clearance of cellular components is particularly important and essential for maintaining neuronal health. Their investigation shed a light on the cause of neurodegenerative disease.  

References:

1.         Komatsu, M. et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol 169, 425-34 (2005).

2.         Kuma, A. et al. The role of autophagy during the early neonatal starvation period. Nature 432, 1032-6 (2004).