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

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. © 2012 kandimalla et al; licensee biomed central ltd.