%0 Journal Article
%T siRNA against presenilin 1 (PS1) down regulates amyloid ¦Â42 production in IMR-32 cells
%A Ramesh JL Kandimalla
%A Willayat Wani
%A Binukumar BK
%A Kiran Gill
%J Journal of Biomedical Science
%D 2012
%I BioMed Central
%R 10.1186/1423-0127-19-2
%X 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 A¦Â42 in IMR-32 Cells using RTPCR, western blotting and immunofluorescence techniques.The results of the present study showed down regulation of PS1 and A¦Â42 in IMR32 cells transfected with siRNA against PS1.Our results substantiate the concept that PS1 is involved in ¦Ã-secretase activity and provides the rationale for therapeutic strategies aimed at influencing A¦Â42 production.A key step in the pathogenesis of AD is proteolysis of APP that results in the formation of the amyloid-¦Â protein (A¦Â), the principle protein component of the characteristic cerebral plaques of the disease [1]. A¦Â is produced from APP £¿rst by the action of ¦Â- secretase, a membrane-tethered enzyme that resembles pepsin and other water-soluble aspartyl proteases [2]. This proteolysis leads to membrane shedding of the large luminal/extracellular APP domain. The 99-residue membrane-bound remnant is then cleaved in the middle of its transmembrane region by ¦Ã -secretase, releasing A¦Â and again near the inner lea£¿et at the ¦Â site to release the APP intracellular domain (AICD) [3]. Rare mutations in the APP gene, found in and around the A¦Â region cause familial early-onset Alzheimer's disease (EOAD) and these mutations alter the production of A¦Â or its aggregation properties [4]. Several contemporaneous observations provided critical clues for the identi£¿cation of the elusive ¦Ã-secretase. First, genes encoding the multi-pass membrane proteins presenilin-1 and presenilin-2 (PS1&PS2) were discovered in a search to identify other genes associated with familial EOAD. The disease-causing missense mutations were soon found to alter how ¦Ã -secretase cuts APP leading to increased proportions of longer, more aggregation-prone forms of A¦Â [5]. Second, knock out of PS-1 dramatically reduced ¦Ã -secretase cleavage of APP [6]. Third, the types of compounds that
%K Alzheimer's Disease
%K presenilins
%K siRNA
%K A¦Â42
%K IMR-32 Cells
%U http://www.jbiomedsci.com/content/19/1/2