Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation.
Nat Med
; 10(9): 959-65, 2004 Sep.
Article
em En
| MEDLINE
| ID: mdl-15286784
ABSTRACT
Inhibiting the activity of the beta-amyloid converting enzyme 1 (BACE1) or reducing levels of BACE1 in vivo decreases the production of amyloid-beta. The reticulon family of proteins has four members, RTN1, RTN2, RTN3 and RTN4 (also known as Nogo), the last of which is well known for its role in inhibiting neuritic outgrowth after injury. Here we show that reticulon family members are binding partners of BACE1. In brain, BACE1 mainly colocalizes with RTN3 in neurons, whereas RTN4 is more enriched in oligodendrocytes. An increase in the expression of any reticulon protein substantially reduces the production of Abeta. Conversely, lowering the expression of RTN3 by RNA interference increases the secretion of Abeta, suggesting that reticulon proteins are negative modulators of BACE1 in cells. Our data support a mechanism by which reticulon proteins block access of BACE1 to amyloid precursor protein and reduce the cleavage of this protein. Thus, changes in the expression of reticulon proteins in the human brain are likely to affect cellular amyloid-beta and the formation of amyloid plaques.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Regulação da Expressão Gênica
/
Peptídeos beta-Amiloides
/
Ácido Aspártico Endopeptidases
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Proteínas de Membrana
/
Proteínas do Tecido Nervoso
Limite:
Humans
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos