title: Attenuated presenilin-1 endoproteolysis enhances store-operated calcium currents in neuronal cells.
abstract: Presenilins have been reported to regulate calcium homeostasis in the endoplasmic reticulum, and dysregulation of intracellular calcium has been implicated in the pathogenesis of Alzheimer's disease (AD). Reduced endoproteolysis levels of presenilin-1 (PS1) have been detected in postmortem brains of patients carrying familial Alzheimer's disease PS1 mutations. This study deals with the effect of attenuated endoproteolysis of PS1 on store-operated calcium (SOC) entry in neuronal cells and mouse fibroblasts with double knockouts of PS1 and PS2. Significant enhancement of SOC channel activation has been detected by electrophysiological measurements in cells with reduced PS1 endoproteolysis. The increase in SOC entry was not accompanied by any changes in protein levels of channels subunits or stromal interaction molecule. These data are important for understanding the role of PS1 in AD, apart from its involvement in γ-secretase cleavage of amyloid precursor protein into Aβ. Taking into account that most of familial AD-connected mutations in PS1 are loss-of-function, the observed effects may well be general for familial AD. Reduced endoproteolysis levels of presenilin-1 (PS1) have been detected in postmortem brains of patients carrying familial Alzheimer's disease PS1 mutations. Significant enhancement of SOC channel activation has been detected by electrophysiological measurements in cells with reduced PS1 endoproteolysis. The data obtained shed light on Alzheimer's disease pathogenesis and implicates to the future drugs development.
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
authors.forename: Maria
authors.initials: M
authors.lastname: Ryazantseva
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
authors.forename: Ksenia
authors.initials: K
authors.lastname: Skobeleva
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
authors.forename: Lyubov
authors.initials: L
authors.lastname: Glushankova
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Kaznacheyeva
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism*; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D053766:Presenilin-2; D053829:Amyloid Precursor Protein Secretases; D002118:Calcium
keywords: Alzheimer's disease; I
  SOC; SOC; endoproteolysis; presenilin; store-operated calcium channels