Linked Life Data

21482951

Source:http://linkedlifedata.com/resource/pubmed/id/21482951

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2011-4-12
pubmed:abstractText
The present review highlights an association between autism, Alzheimer disease (AD), and fragile X syndrome (FXS). We propose a conceptual framework involving the amyloid-? peptide (A?), A? precursor protein (APP), and fragile X mental retardation protein (FMRP) based on experimental evidence. The anabolic (growth-promoting) effect of the secreted ? form of the amyloid-? precursor protein (sAPP?) may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPP? levels associate with more severe symptoms of autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 (mGluR5). Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPP? level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPP? and production of insoluble A? would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1526-632X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1344-52
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links.
pubmed:affiliation
Department of Neurology, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202, USA.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural