- 作者: Ramesh JL Kandimalla, Willayat YOUSUF Wani, Binukumar Bk, Kiran DIP Gill
- 作者服務機構: Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India
- 中文摘要: --
- 英文摘要:
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. - 中文關鍵字: --
- 英文關鍵字: Alzheimer’s Disease, presenilins, siRNA, Aβ42, IMR-32 Cells