Patient-Specific iPSC-Based Models of Huntington's Disease as a Tool to Study Store-Operated Calcium Entry Drug Targeting

Frontiers in Pharmacology
Vladimir VigontElena Kaznacheyeva

Abstract

Neurodegenerative pathologies are among the most serious and socially significant problems of modern medicine, along with cardiovascular and oncological diseases. Several attempts have been made to prevent neuronal death using novel drugs targeted to the cell calcium signaling machinery, but the lack of adequate models for screening markedly impairs the development of relevant drugs. A potential breakthrough in this field is offered by the models of hereditary neurodegenerative pathologies based on endogenous expression of mutant proteins in neurons differentiated from patient-specific induced pluripotent stem cells (iPSCs). Here, we study specific features of store-operated calcium entry (SOCE) using an iPSCs-based model of Huntington's disease (HD) and analyze the pharmacological effects of a specific drug targeted to the calcium channels. We show that SOCE in gamma aminobutyric acid-ergic striatal medium spiny neurons (GABA MSNs) was mediated by currents through at least two different channel groups, ICRAC and ISOC. Both of these groups were upregulated in HD neurons compared with the wild-type neurons. Thapsigargin-induced intracellular calcium store depletion in GABA MSNs resulted in predominant activation of either ICRAC ...Continue Reading

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Citations

Nov 30, 2018·Biomolecules & Therapeutics·Hyun-Jung Kim
Dec 4, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Swati NaphadeLisa M Ellerby
Jun 13, 2020·Frontiers in Cell and Developmental Biology·Anna SlanziGabriela Constantin
Jul 28, 2019·Bulletin of Experimental Biology and Medicine·K O GusevE V Kaznacheeva
Dec 18, 2020·Frontiers in Cellular Neuroscience·Isis Zhang, Huijuan Hu
Jan 12, 2021·Frontiers in Cell and Developmental Biology·Magdalena Czeredys
Feb 20, 2021·Frontiers in Cell and Developmental Biology·Vladimir A VigontElena V Kaznacheyeva

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Methods Mentioned

BETA
biopsies
biopsy

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