Linked Life Data

17331621

Source:http://linkedlifedata.com/resource/pubmed/id/17331621

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-4-28
pubmed:abstractText
Accumulation of cerebral amyloid-beta (Abeta) has been implicated as a putative causal factor in the development of Alzheimer's disease (AD). Transgenic mice like the PDAPP line overexpress human mutant Amyloid Precursor Protein (hAPP) and recapitulate many features of AD, including amyloid neuropathology and cognitive deficits. Inhibition of the beta-site aspartyl cleaving enzyme (BACE1) enzyme responsible for the first proteolytic cleavage that ultimately generates Abeta has been proposed as a strategy for AD therapy. To assess the theoretical repercussions of beta-secretase activity reduction in an in vivo model of AD, BACE1(-/-) mice bred to the PDAPP line were examined in a series of behavioral tasks. Although BACE1 gene ablation abolished hAbeta accumulation, BACE1(-/-) mice had unexpected sensorimotor impairments, spatial memory deficits, and displayed seizures, phenotypes which were severe on the PDAPP background. These results suggest that while excess Abeta is functionally pathological, BACE1-mediated processing of APP and other substrates play a role in "normal" learning, memory and sensorimotor processes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1558-1497
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
861-73
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
BACE1 gene deletion: impact on behavioral function in a model of Alzheimer's disease.
pubmed:affiliation
Rinat Neurosciences, 230 East Grand Avenue, South San Francisco, CA 94080, USA. dkobayashi@rinatneuro.com
pubmed:publicationType
Journal Article