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Cell-Autonomous Death of Cerebellar Purkinje Neurons with Autophagy in Niemann-Pick Type C Disease
Jul 25, 2005, 17:13, Reviewed by: Dr.
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The researchers also found that the degenerating PCs undergo a complex process called autophagy in which the cells sense a lack of key nutrients and start to break down their own structures to feed themselves.
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By PLoS Genetics,
Niemann-Pick disease type C is a deadly neurodegenerative disease that is most often due to mutations in a gene called npc1. As a consequence of intracellular lipid trafficking defects, patients with Niemann-Pick type C, and mice with the same disease, lose an important class of cerebellar neurons called Purkinje cells (PCs).
Npc1 (the protein coded by npc1) might be needed in other cell types to produce substances that nourish PCs or within the PCs themselves. To see which is true, the researchers constructed genetically mosaic mice in which some cells have mutant Npc1 and some have normal Npc1 function.
In the cerebella of these mosaic mice, PCs lacking Npc1 continued to die even while surrounded by normal cells, while normal PCs appeared unaffected by their partially mutant surroundings. From these findings, the researchers concluded that the neurodegeneration is due to a problem within PCs and not due to a lack of supporting factors provided by other cells or an extrinsic toxic or inflammatory insult. Npc1 probably functions within PCs to allow critical transport processes necessary for cell survival.
The researchers also found that the degenerating PCs undergo a complex process called autophagy in which the cells sense a lack of key nutrients and start to break down their own structures to feed themselves.
By identifying exactly which cells require Npc1 function, the researchers set the stage for investigating the exact molecular roles of Npc1 protein in the cells where it is most needed. 
- Ko DC, Milenkovic L, Beier SM, Manuel H, Buchanan J, et al. (2005) Cell-Autonomous Death of Cerebellar Purkinje Neurons with Autophagy in Niemann-Pick Type C Disease. PLoS Genet 1(1): e7
PDF of Article
DOI: 10.1371/journal.pgen.0010007
Copyright: � 2005 Ko et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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