Linked Life Data

20219645

Source:http://linkedlifedata.com/resource/pubmed/id/20219645

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-4-13
pubmed:abstractText
Doppel protein (Dpl) is a paralog of the cellular form of prion protein (PrP(C)). Its ectopic expression in the CNS elicits significant cerebellar Purkinje cell degeneration in some lines of PrP knockout mice. However, little is known about the Dpl-mediated neurodegenerative mechanism. To understand the molecular and intracellular pathways underlying Purkinje cell degeneration, here, we investigated the regulation of calcium-release channel protein, type 1 inositol 1,4,5-trisphosphate receptor (IP(3)R1) gene in Ngsk mice. These knockout mice express high levels of Dpl and eventually develop cerebellar degeneration. We observed that the expression level of IP(3)R1 gene is reduced in the cerebella of Ngsk mice as early as 3 months of age compared with age-matched controls along with the reduction in DNA binding activity of nuclear factor of activated-T cells (NFAT) which is transcription factor of IP(3)R1. Notably, expression of PrP restored the reduced DNA binding activity of NFATc4 by Dpl. Reduced expressions of brain-derived neurotrophic factor (BDNF) and ionotropic glutamate receptor subtype 2 or B (GluR2), which are regulated by NFATc4, were also restored by PrP expression. In light of these findings, we suggest a mechanism for Dpl-mediated Purkinje cell degeneration linked to reduced gene expression of proteins related to neuronal activity. Decrease in IP(3)R1 gene expression may lead to functional deficits and ultimately death of Purkinje cells in Ngsk mice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1873-7544
pubmed:author
pubmed:copyrightInfo
Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
167
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
799-808
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Altered expression of type 1 inositol 1,4,5-trisphosphate receptor in the Ngsk Prnp deficient mice.
pubmed:affiliation
Ilsong Institute of Life Science, Hallym University, Anyang, Dongan-gu, Gyeonggi-Do, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't