Linked Life Data

20645406

Source:http://linkedlifedata.com/resource/pubmed/id/20645406

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2010-9-21
pubmed:abstractText
Charcot-Marie-Tooth (CMT) disease is the most frequent peripheral neuropathy affecting the Schwann cells and neurons. CMT disease type 2 (CMT2) neuropathies are characterized by peripheral nerve aberrance. Four missense mutations of Rab7, a small GTPase of the Rab family involved in intracellular vesicular trafficking, are associated with the CMT2B phenotype. Despite a growing body of evidence concerning the gene structures responsible for genetically heterogenous CMT2B and other CMT2 neuropathies, little is known about the in vitro neuropathy model and how CMT2B-associated mutation-caused aberrant neuritogenesis is properly reversed. Here, we show that valproic acid (VPA), a classical mood-stabilizing drug, improves defective neurite formation in N1E-115 neuroblastoma cells regardless of which CMT2B-associated Rab7 mutant protein is expressed. The effect is mediated by c-Jun N-terminal kinase (JNK) signaling, but not by deacetylase inhibition activity of VPA itself. Furthermore, VPA has similar effects in dorsal root ganglion (DRG) neurons expressing any of the four mutant Rab7 proteins. Thus, VPA has a previously unknown potential to improve defective neuritogenesis associated with CMT2B in vitro, indicating that JNK should be a potential therapeutic target for treatments aimed at improving neuritogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1097-4547
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3189-97
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The mood stabilizer valproic acid improves defective neurite formation caused by Charcot-Marie-Tooth disease-associated mutant Rab7 through the JNK signaling pathway.
pubmed:affiliation
Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan. jyamauchi@nch.go.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't