STIM1, STIM2 and Orai1-overexpression of key store operated calcium entry in transgenic mice brain

• Autorzy: Majewski L. , Wiera G. , Wojtowicz T. , Boguszewski P.M. , Mozrzymas J. , Kuznicki J.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. At least two types of AD can be distinguished: sporadic AD (SAD) of unknown etiology, which accounts for most cases, and genetically encoded familial AD (FAD), which affects up to 5% of all patients. Altered calcium homeostasis in neurons is proposed to be one of the early events responsible for AD. Disturbances in Ca2+ signaling are found in SAD patients before any obvious extracellular Aβ pathology; moreover, Ca2+ dysfunction augments Aβ formation and Tau hyperphosphorylation. One of the objectives of our present project is to understand how elevated basal Ca2+ level in neurons contributes to neurodegeneration. METHODS: Generation of transgenic mice using DNAmicroinjection technique. RESULTS: We have generated three transgenic mouse lines independently overexpressing,specifically in brain neurons, key proteins of SOCE – STIM1, STIM2 and Orai1. The phenotype of these mice is being analyzed by electrophysiology, behavior and Ca2+ imaging. Our group has shown that the cytoplasmic resting Ca2+ level in cultured neurons can be modulated by overexpression of STIM proteins, ER Ca2+ sensors involved in the Store Operated Calcium Entry (SOCE). We also detected the enhanced magnitude of Ca2+ influx during SOCE in human lymphocytes from SAD patients, and decreased level of STIM2 protein in human lymphocytes from FAD patients in parallel to an attenuation of SOCE. CONCLUSIONS: The obtained lines can be a suitable model to verify the hypothesis that brain dysfunction during ageing is induced by changes in Ca2+ homeostasis.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S42

Twórcy

autor

Majewski L.

• Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland

autor

Wiera G.

• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Wojtowicz T.

• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Boguszewski P.M.

• Laboratory of Limbic System, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Mozrzymas J.

• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Kuznicki J.

• Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland