siRNA against presenilin 1 (PS1) down regulates amyloid ß42 production in IMR-32 cells.
J Biomed Sci
; 19: 2, 2012 Jan 03.
Article
em En
| MEDLINE
| ID: mdl-22214483
ABSTRACT
BACKGROUND:
One of the pathological hallmarks of Alzheimer's disease (AD) is the deposition of the ~4 kDa amyloid ß protein (Aß) within lesions known as senile plaques. Aß is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Aß that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a ß-pleated-sheet conformation and deposited extracellularly in the form of 5-10 nm wide straight fibrils. As γ-secretase catalyzes the final cleavage that releases the Aß42 or 40 from amyloid ß -protein precursor (APP), therefore, it is a potential therapeutic target for the treatment of AD. γ-Secretase cleavage is performed by a high molecular weight protein complex containing presenilins (PSs), nicastrin, Aph-1 and Pen-2. Previous studies have demonstrated that the presenilins (PS1 and PS2) are critical components of a large enzyme complex that performs γ-secretase cleavage.METHODS:
In this study we used RNA interference (RNAi) technology to examine the effects of small-interfering RNA (siRNA) against PS1 on expression levels of PS1 and Aß42 in IMR-32 Cells using RTPCR, western blotting and immunofluorescence techniques.RESULTS:
The results of the present study showed down regulation of PS1 and Aß42 in IMR32 cells transfected with siRNA against PS1.CONCLUSION:
Our results substantiate the concept that PS1 is involved in γ-secretase activity and provides the rationale for therapeutic strategies aimed at influencing Aß42 production.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação para Baixo
/
Peptídeos beta-Amiloides
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RNA Interferente Pequeno
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Secretases da Proteína Precursora do Amiloide
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Presenilina-1
Limite:
Humans
Idioma:
En
Revista:
J Biomed Sci
Assunto da revista:
MEDICINA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Índia