Beta- but not gamma-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• Beta- but not gamma-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia (Articolo in rivista) (literal)

Anno

• 2012-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1002/emmm.201100195 (literal)

Alternative label

• Tamayev Robert1; Matsuda Shuji1; Arancio Ottavio2; D'Adamio Luciano1,3 (2012)
  Beta- but not gamma-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia
  in EMBO molecular medicine (Print)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Tamayev Robert1; Matsuda Shuji1; Arancio Ottavio2; D'Adamio Luciano1,3 (literal)

Pagina inizio

• 171 (literal)

Pagina fine

• 179 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni

• Epub 2012 Jan 23. (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 4 (literal)

Rivista

• EMBO molecular medicine (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

• 8 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

• 3 (literal)

Note

• PubMe (literal)
• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• 1 Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA. 2 Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York,NY, USA. 3 Institute of Cellular Biology and Neurobiology, National Council of Research of Rome, Rome, Italy. (literal)

Titolo

• Beta- but not gamma-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia (literal)

Abstract

• A mutation in the BRI2/ITM2b gene causes loss of BRI2 protein leading to familial Danish dementia (FDD). BRI2 deficiency of FDD provokes an increase in amyloid-beta precursor protein (APP) processing since BRI2 is an inhibitor of APP proteolysis, and APP mediates the synaptic/memory deficits in FDD. APP processing is linked to Alzheimer disease (AD) pathogenesis, which is consistent with a common mechanism involving toxic APP metabolites in both dementias. We show that inhibition of APP cleavage by beta-secretase rescues synaptic/memory deficits in a mouse model of FDD. Beta-cleavage of APP yields amino-terminal-soluble APP beta (sAPPbeta) and beta-carboxyl-terminal fragments (beta-CTF). Processing of beta-CTF by gamma-secretase releases amyloid-beta (A beta), which is assumed to cause AD. However, inhibition of gamma-secretase did not ameliorate synaptic/memory deficits of FDD mice. These results suggest that sAPP beta and/or beta-CTF, rather than ABeta, are the toxic species causing dementia, and indicate that reducing beta-cleavage of APP is an appropriate therapeutic approach to treating human dementias. Our data and the failures of anti-ABeta therapies in humans advise against targeting gamma-secretase cleavage of APP and/or A Beta. (literal)

Prodotto di

• ex ME.P02.010.001 / Patologie del S.N. e Fattori di Crescita (ME.P02.010.004) (Modulo)

Autore CNR

• Luciano D'Adamio (Unità di personale esterno)

Insieme di parole chiave

• Parole chiave di "Beta- but not gamma-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia" (Insieme di parole chiave)

Incoming links:

Prodotto

• ex ME.P02.010.001 / Patologie del S.N. e Fattori di Crescita (ME.P02.010.004) (Modulo)

Autore CNR di

• Luciano D'Adamio (Unità di personale esterno)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• EMBO molecular medicine (Rivista)

Insieme di parole chiave di

• Parole chiave di "Beta- but not gamma-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia" (Insieme di parole chiave)