Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 29, Pages 7717-7730Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1254-07.2007
Keywords
myelin; oligodendrocyte; cytoskeleton; neurodegeneration; Pelizaeus-Merzbacher disease; hereditary spastic paraplegia; NAD(+)/ NADH; acetylation; metabolism
Categories
Funding
- NINDS NIH HHS [R01 NS042925-05A1, R01 NS042925, NS042925, R37 NS042925] Funding Source: Medline
Ask authors/readers for more resources
Mice lacking the expression of proteolipid protein (PLP)/DM20 in oligodendrocytes provide a genuine model for spastic paraplegia (SPG-2). Their axons are well myelinated but exhibit impaired axonal transport and progressive degeneration, which is difficult to attribute to the absence of a single myelin protein. Wehypothesized that secondary molecular changes in PLPnull myelin contribute to the loss of PLP/DM20-dependent neuroprotection and provide more insight into glia-axonal interactions in this disease model. By gel-based proteome analysis, we identified >160 proteins in purified myelin membranes, which allowed us to systematically monitor the CNS myelin proteome of adult PLPnull mice, before the onset of disease. We identified three proteins of the septin family to be reduced in abundance, but the nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase sirtuin 2 (SIRT2) was virtually absent. SIRT2 is expressed throughout the oligodendrocyte lineage, and immunoelectron microscopy revealed its association with myelin. Loss of SIRT2 in PLPnull was posttranscriptional, suggesting that PLP/DM20 is required for its transport into the myelin compartment. Because normal SIRT2 activity is controlled by the NAD(+)/NADH ratio, its functionmaybe coupled to the axo-glial metabolism and the long-term support of axons by oligodendrocytes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available