Linked Life Data

21431475

Source:http://linkedlifedata.com/resource/pubmed/id/21431475

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-3-24
pubmed:abstractText
The mediator neuroprotectin D1 (NPD1) is an enzymatic derivative of the omega-3 essential fatty acid docosahexaenoic acid. NPD1 stereoselectively and specifically binds to human retinal pigment epithelium (RPE) cells and neutrophils. In turn, this lipid mediator induces dephosphorylation of Bcl-x(L) in a PP2A-dependent manner and induces PI3K/Akt and mTOR/p70S6K pathways leading to RPE cell survival during oxidative stress-induced apoptosis. As a proof of principle of its systemic in vivo bioactivity, NPD1 attenuates laser-induced choroidal neovascularization in mice. Using human neural cells transfected with amyloid precursor protein (APP)sw (Swedish double mutation APP695sw, K595N, M596L), NPD1 was shown to regulate secretase-mediated production of A? peptide, downregulates pro-inflammatory gene expression, and promotes cell survival. In human neural cells overexpressing beta-amyloid precursor protein (?APP), the lipid mediator suppressed A?42 shedding by downregulating ?-secretase (BACE1) while activating the ?-secretase (ADAM10), thus shifting the ?APP cleavage from the noxious amyloidogenic pathway into a non-amyloidogenic, neurotrophic pathway. Furthermore, downregulation of A?42 peptide release by NPD1 may be dependent upon PPAR? activation. In conclusion, NPD1 exhibits anti-inflammatory, anti-amyloidogenic, and anti-apoptotic bioactivities in human neural cells in part via PPAR? signaling and through the targeting of ?- and ?-secretase systems.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1559-1182
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
131-8
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Neuroprotectin D1 induces neuronal survival and downregulation of amyloidogenic processing in Alzheimer's disease cellular models.
pubmed:affiliation
Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, USA.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural