RGD Reference Report - Fas and Fas ligand are associated with neuritic degeneration in the AD brain and participate in beta-amyloid-induced neuronal death. - Rat Genome Database

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Fas and Fas ligand are associated with neuritic degeneration in the AD brain and participate in beta-amyloid-induced neuronal death.

Authors: Su, JH  Anderson, AJ  Cribbs, DH  Tu, C  Tong, L  Kesslack, P  Cotman, CW 
Citation: Su JH, etal., Neurobiol Dis. 2003 Apr;12(3):182-93.
RGD ID: 8663481
Pubmed: PMID:12742739   (View Abstract at PubMed)

It has recently been suggested that neuronal cell death in response to many brain insults may be mediated by the upregulation of tumor necrosis factor receptor (TNFR) family members and their ligands. In the present study, we investigated whether the expression of the TNFR family death domain receptor, Fas, and its ligand, FasL, is altered in association with neuropathology and activated caspase markers in Alzheimer disease (AD) brain, and Abeta-induced neuronal cell death in vitro. To evaluate this hypothesis, we examined Fas and FasL expression in AD and control brain, and Abeta-treated primary neurons, using immunocytochemistry and Western blots. Neurons in both AD brain and Abeta-treated cultures exhibited FasL upregulation and changes in immunoreactivity for Fas receptor. Further, FasL expression was remarkably elevated in senile plaques and neurofilament-positive dystrophic neurites, and in association with caspase activation and neuritic apoptosis in AD brain. Based on these and previous data regarding protection of primary neuronal cultures from Abeta(1-42)-induced apoptosis by blockade of Fas-associated death domain signaling, we also tested the hypothesis that dynamic regulation of Fas and FasL may contribute to Abeta-mediated neuronal cell death. Accordingly, neuronal cultures derived from mice carrying inactivating mutations in Fas (Faslpr) or FasL (Fasgld) exhibited protection from Abeta(1-42)-induced cell death. These findings suggest that Fas-FasL interactions may contribute to mechanisms of neuronal loss and neuritic degeneration in AD.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  IEP 8663481protein:increased expression:brain and plaque (human)RGD 
Alzheimer's disease  ISOFAS (Homo sapiens)8663481; 8663481protein:increased expression:brain and plaque (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fas  (Fas cell surface death receptor)

Genes (Mus musculus)
Fas  (Fas cell surface death receptor)

Genes (Homo sapiens)
FAS  (Fas cell surface death receptor)


Additional Information