Role of store operated calcium entry in neurons

• Autorzy: Kuznicki J.
• Języki publikacji: EN

Abstrakty

EN

The number of people with neurodegenerative and psychiatric diseases is expanding globally. Unfortunately, there are no treatments, which can delay the progress of Alzheimer’s disease (AD), no new drugs with fewer side-effects on Parkinson’s disease (PD), Huntington’s disease (HD) and depression (MDD), no drugs for patients resistant to the existing MDD therapies. Moreover, in most diseases there are no reliable biomarkers for presymptomatic diagnosis and monitoring of effects of therapeutic treatments. Therefore, there is a growing need for better understanding of the basis of neurodegenerative and psychiatric diseases, identification of drug targets and new biomarkers, and development of new treatments and drugs. Altered Ca2+ 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, and Ca2+ dysfunction augments Aβ formation and Tau hyperphosphorylation. Dysregulation of Ca2+ homeostasis and signaling has been also observed in PD, HD and some psychiatric diseases. GWAS analysis identified specific SNPs in two voltage-gated calcium channels associated with a range of psychiatric disorders. We detected the enhanced magnitude of Ca2+ influx during Store Operated Calcium Entry (SOCE) in human lymphocytes from SAD patients, and decreased level of STIM2 from FAD patients in parallel to an attenuation of SOCE. The decreased level of STIM2 in AD models and brains of AD patients was confirmed by other authors. We also showed that the cytoplasmic resting Ca2+ level in cultured neurons can be modulated by overexpression of SOCE proteins (STIM1, STIM2 or Orai1). Based on our and literature data I will describe the role of SOCE in neurons and its perturbation in neurological diseases. To conclude, the SOCE proteins can be considered as new drug targets for some of these diseases and that dysregulation of SOCE might be used for diagnostic purposes.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S27

Twórcy

autor

Kuznicki J.

• International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland