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

Ramesh J.L. Kandimalla, Willayat Wani, Binukumar Bk, Kiran Gill*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish (US)
Article number2
JournalJournal of Biomedical Science
Issue number1
StatePublished - 2012


  • Alzheimer's Disease
  • Aββ42
  • IMR-32 Cells
  • presenilins
  • siRNA

ASJC Scopus subject areas

  • Biochemistry, medical
  • Pharmacology (medical)
  • Molecular Biology
  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism
  • Cell Biology


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