Linked Life Data

11487626

Source:http://linkedlifedata.com/resource/pubmed/id/11487626

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2001-8-6
pubmed:abstractText
Previous studies have shown that transgenic (Tg) mice overexpressing human tau protein develop filamentous tau aggregates in the CNS. The most abundant tau aggregates are found in spinal cord and brainstem in which they colocalize with neurofilaments (NFs) as spheroids in axons. To elucidate the role of NF subunit proteins in tau aggregate formation and to test the hypothesis that NFs are pathological chaperones in the formation of intraneuronal tau inclusions, we crossbred previously described tau (T44) Tg mice overexpressing the smallest human tau isoform with knock-out mice devoid of NFL (NFL-/-) or NFH (NFH-/-). Depletion of NF subunit proteins from the T44 mice (i.e., T44;NFL-/- and T44;NFH-/-), in particular NFL, resulted in a dramatic decrease in the total number of tau-positive spheroids in spinal cord and brainstem. Concomitant with the reduction in spheroid number, the bigenic mice showed delayed accumulation of insoluble tau protein in the CNS, increased viability, reduced weight loss, and improved behavioral phenotype when compared with the single T44 Tg mice. These results imply that NFs are pathological chaperones in the development of tau spheroids and suggest a role for NFs in the pathogenesis of neurofibrillary tau lesions in neurodegenerative disorders that contain both NFs and tau proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6026-35
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Attenuated neurodegenerative disease phenotype in tau transgenic mouse lacking neurofilaments.
pubmed:affiliation
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't