Linked Life Data

15465426

Source:http://linkedlifedata.com/resource/pubmed/id/15465426

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2004-10-6
pubmed:abstractText
Genetic deficiency of NPC1 or NPC2 results in a devastating cholesterol-glycosphingolipidosis of brain and other organs known as Niemann-Pick type C (NPC) disease. While NPC1 is a transmembrane protein believed involved in retroendocytic shuttling of substrate(s) to the Golgi and possibly elsewhere in cells as part of an essential recycling/homeostatic control mechanism, NPC2 is a soluble lysosomal protein known to bind cholesterol. The precise role(s) of NPC1 and NPC2 in endosomal-lysosomal function remain unclear, nor is it known whether the two proteins directly interact as part of this function. The pathologic features of NPC disease, however, are well documented. Brain cells undergo massive intracellular accumulation of glycosphingolipids (lactosylceramide, glucosylceramide, GM2 and GM3 gangliosides) and cholesterol and concomitant distortion of neuron shape (meganeurite formation). In neurons from humans with NPC disease the metabolic defects and storage often lead to extensive growth of new, ectopic dendrites (possibly linked to ganglioside sequestration) as well as formation of neurofibrillary tangles (NFTs) (possibly linked to dysregulation of cholesterol metabolism). Other features of cellular pathology in NPC disease include fragmentation of the Golgi apparatus and neuroaxonal dystrophy, though reasons for these changes remain largely unknown. As the disease progresses, neurodegeneration is also apparent for neurons in some brain regions, particularly Purkinje cells of the cerebellum, but the basis of this selective neuronal vulnerability is unknown. The NPC1 protein is evolutionarily conserved with homologues reported in yeast to humans; NPC2 is reported in C. elegans to humans. While neurons in mammalian models of NPC1 and NPC2 diseases exhibit many changes that are remarkably similar to those in humans (e.g., endosomal/lysosomal storage, Golgi fragmentation, neuroaxonal dystrophy, neurodegeneration), a reduced degree of ectopic dendritogenesis and an absence of NFTs in these species suggest important differences in the way lower mammalian neurons respond to NPC1/NPC2 loss of function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
1685
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
48-62
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Consequences of NPC1 and NPC2 loss of function in mammalian neurons.
pubmed:affiliation
Sidney Weisner Laboratory of Genetic Neurological Disease Department of Neuroscience, Rose F Kennedy Center for Research in Mental Retardation and Human Development, Albert Einstein College of Medicine, Bronx, NY 10461, USA. walkley@aecom.yu.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't