Linked Life Data

15336977

Source:http://linkedlifedata.com/resource/pubmed/id/15336977

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-8-31
pubmed:abstractText
Huntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). HD is caused by polyglutamine (polyQ) expansion (exp) in the amino-terminal region of a protein huntingtin (Htt). The connection between polyQ expansion in Httexp and MSN neurodegeneration remains elusive. Here we discuss recent data that link polyQ expansion in Httexp and deranged Ca2+ signaling in MSN neurons. Experimental evidence indicates that (1) Ca2+ homeostasis is abnormal in mitochondria isolated from lymphoblasts of HD patients and from brains of the YAC72 HD mouse model; (2) Httexp leads to potentiation of NR1/NR2B NMDA receptor activity in heterologous expression systems and in MSN from YAC72 HD mouse model; and (3) Httexp binds to the type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1) carboxy-terminus and causes sensitization of InsP3R1 to activation by InsP3 in planar lipid bilayers and in MSN. Based on these results we propose that Httexp-induced cytosolic and mitochondrial Ca2+ overload of MSN plays an important role in the pathogenesis of HD and that Ca2+ signaling blockers may play a beneficial role in treatment of HD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-291X
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Elsevier Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
322
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1310-7
pubmed:dateRevised
2007-7-18
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Deranged neuronal calcium signaling and Huntington disease.
pubmed:affiliation
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. Ilya.Bezprozvanny@UTSouthwestern.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't