Linked Life Data

18591368

Source:http://linkedlifedata.com/resource/pubmed/id/18591368

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2008-10-1
pubmed:abstractText
Niemann-Pick type C (NPC) disease is a fatal autosomal recessive disorder characterized by the accumulation of free cholesterol and glycosphingolipids in the endosomal-lysosomal system. Patients with NPC disease have markedly progressive neuronal loss, mainly of cerebellar Purkinje neurons. There is strong evidence indicating that cholesterol accumulation and trafficking defects activate apoptosis in NPC brains. The purpose of this study was to analyze the relevance of apoptosis and particularly the proapoptotic c-Abl/p73 system in cerebellar neuron degeneration in NPC disease. We used the NPC1 mouse model to evaluate c-Abl/p73 expression and activation in the cerebellum and the effect of therapy with the c-Abl-specific inhibitor imatinib. The proapoptotic c-Abl/p73 system and the p73 target genes are expressed in the cerebellums of NPC mice. Furthermore, inhibition of c-Abl with imatinib preserved Purkinje neurons and reduced general cell apoptosis in the cerebellum, improved neurological symptoms, and increased the survival of NPC mice. Moreover, this prosurvival effect correlated with reduced mRNA levels of p73 proapoptotic target genes. Our results suggest that the c-Abl/p73 pathway is involved in NPC neurodegeneration and show that treatment with c-Abl inhibitors is useful in delaying progressive neurodegeneration, supporting the use of imatinib for clinical treatment of patients with NPC disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3617-27
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18591368-Animals, pubmed-meshheading:18591368-Apoptosis, pubmed-meshheading:18591368-Cell Survival, pubmed-meshheading:18591368-Cerebellar Cortex, pubmed-meshheading:18591368-DNA-Binding Proteins, pubmed-meshheading:18591368-Disease Models, Animal, pubmed-meshheading:18591368-Gene Expression, pubmed-meshheading:18591368-Mice, pubmed-meshheading:18591368-Mice, Knockout, pubmed-meshheading:18591368-Motor Activity, pubmed-meshheading:18591368-Niemann-Pick Disease, Type C, pubmed-meshheading:18591368-Nuclear Proteins, pubmed-meshheading:18591368-Piperazines, pubmed-meshheading:18591368-Proteins, pubmed-meshheading:18591368-Proto-Oncogene Proteins c-abl, pubmed-meshheading:18591368-Purkinje Cells, pubmed-meshheading:18591368-Pyrimidines, pubmed-meshheading:18591368-RNA, Messenger, pubmed-meshheading:18591368-Tumor Suppressor Proteins
pubmed:year
2008
pubmed:articleTitle
Imatinib therapy blocks cerebellar apoptosis and improves neurological symptoms in a mouse model of Niemann-Pick type C disease.
pubmed:affiliation
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, casilla 114-D, Santiago, Chile. aalvarez@bio.puc.cl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't