siRNA against presenilin 1 (PS1) down regulates amyloid β42 production in IMR-32 cells

Journal of Biomedical Science

Kiran Dip Gill¹  Binukumar BK¹  Willayat Yousuf Wani¹  Ramesh JL Kandimalla¹ 

[1] Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India

关键词: IMR-32 Cells;    Aβ42;    siRNA;    presenilins;    Alzheimer's Disease;   

Others  :  1146727
DOI  :  10.1186/1423-0127-19-2

 received in 2011-11-20, accepted in 2012-01-03,  发布年份 2012

【 摘 要 】

Background

One of the pathological hallmarks of Alzheimer's disease (AD) is the deposition of the ~4 kDa amyloid β protein (Aβ) within lesions known as senile plaques. Aβ is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Aβ that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a β-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 Aβ42 or 40 from amyloid β -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 Aβ42 in IMR-32 Cells using RTPCR, western blotting and immunofluorescence techniques.

Results

The results of the present study showed down regulation of PS1 and Aβ42 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 Aβ42 production.

【 授权许可】

   
2012 Kandimalla et al; licensee BioMed Central Ltd.

【 图 表 】

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