Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2006-5-17
pubmed:abstractText
Purkinje neurons (PNs), the central cells in cerebellar circuitry and function, constitute a vulnerable population in many human genetic, malignant, hypoxic, and toxic diseases. In the nervous (nr) mutant mouse, the majority of PNs die in the fourth to fifth postnatal weeks, but the responsible molecules are unknown. We first disclose a remarkable increase in mRNA expression and protein concentration in the nr cerebellum of tissue plasminogen activator (tPA), a gene closely linked to the mapped but as-yet-uncloned nr locus. Evidence that excessive tPA triggers nr PN death was obtained with organotypic slice cultures expressing the nr PN phenotype, in which an inhibitor of tPA led to increased nr PN survival. An antagonist of protein kinase C, a downstream component in the tPA pathway, also increased nr PN survival. Additional downstream targets in the tPA pathway (the mitochondrial voltage-dependent anion channel, brain-derived neurotrophic factor, and neurotrophin 3) were also abnormal, in parallel with the alterations in PN mitochondrial morphology, dendritic growth, and synaptogenesis that culminate in nr PN death and motor incoordination. We thus propose a molecular pathway by which the excessive tPA in nr cerebellum mediates PN degeneration.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-10365962, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-10393078, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-10570208, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-11135603, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-11135617, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-1117128, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-11399424, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-11574832, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-11729324, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-11743997, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-11850459, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-11978830, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-12736244, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-12859682, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-12917371, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-14568361, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-14980203, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-15157603, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-15377872, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-15486301, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-15630096, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-15846799, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-16146712, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-16150423, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-16209928, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-3193127, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-3678603, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-4766206, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-7507479, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-7566088, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-7688384, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-7805285, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-8533091, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-9228078, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-9404726, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-9461198, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-9492149, http://linkedlifedata.com/resource/pubmed/commentcorrection/16682647-9545640
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7847-52
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Purkinje neuron degeneration in nervous (nr) mutant mice is mediated by a metabolic pathway involving excess tissue plasminogen activator.
pubmed:affiliation
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural