Viable mouse gene ablations that robustly alter brain Aß levels are rare.
BMC Neurosci
; 11: 143, 2010 Nov 05.
Article
em En
| MEDLINE
| ID: mdl-21054826
ABSTRACT
BACKGROUND:
Accumulation of amyloid-ß (Aß) peptide in the brain is thought to play a key pathological role in Alzheimer's disease. Many pharmacological targets have therefore been proposed based upon the biochemistry of Aß, but not all are equally tractable for drug discovery.RESULTS:
To search for novel targets that affect brain Aß without causing toxicity, we screened mouse brain samples from 1930 novel gene knock-out (KO) strains, representing 1926 genes, using Aß ELISA assays. Although robust Aß lowering was readily apparent in brains from a BACE1 KO strain, none of the novel strains exhibited robust decreases in brain Aß, including a GPR3 KO strain, which had previously been proposed as an Aß target. However, significantly increased Aß was observed in brain samples from two KO strains, corresponding to genes encoding the glycosylphosphatidylinositol mannosyl transferase PIGZ and quinolinate phosphoribosyltransferase (QPRT).CONCLUSIONS:
Thus, gene ablations that are permissive for mouse survival and that also have a robust effect on Aß levels in the brain are rare.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
/
Ácido Aspártico Endopeptidases
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Secretases da Proteína Precursora do Amiloide
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Técnicas de Inativação de Genes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article