Dithiadiazole derivative 3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxide – Novel modulator of store-operated calcium entry

Grekhnev, Dmitriy A.; Novikova, Iuliia V.; Krisanova, Alena V.; Yuskovets, V. N.; Chernov, N. M.; Yakovlev, I. P.; Kaznacheyeva, Еlena; Vigont, Vladimir

doi:10.1016/j.bbrc.2022.08.001

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…Aberrant calcium signaling has been shown in a number of neurodegenerative pathologies including PD, Huntington’s disease (HD), Alzheimer’s disease, spinocerebellar ataxias, etc. [ 42 , 43 ]. In particular, it has been reported that such a ubiquitous pathway for calcium influx as store-operated calcium (SOC) entry (SOCE) plays an important role in HD pathogenesis [ 44 , 45 , 46 , 47 , 48 , 49 ].…”

Section: Resultsmentioning

confidence: 99%

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An Efficient 2D Protocol for Differentiation of iPSCs into Mature Postmitotic Dopaminergic Neurons: Application for Modeling Parkinson’s Disease

Lebedeva

Шарова

Grekhnev

et al. 2023

IJMS

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About 15% of patients with parkinsonism have a hereditary form of Parkinson’s disease (PD). Studies on the early stages of PD pathogenesis are challenging due to the lack of relevant models. The most promising ones are models based on dopaminergic neurons (DAns) differentiated from induced pluripotent stem cells (iPSCs) of patients with hereditary forms of PD. This work describes a highly efficient 2D protocol for obtaining DAns from iPSCs. The protocol is rather simple, comparable in efficiency with previously published protocols, and does not require viral vectors. The resulting neurons have a similar transcriptome profile to previously published data for neurons, and have a high level of maturity marker expression. The proportion of sensitive (SOX6+) DAns in the population calculated from the level of gene expression is higher than resistant (CALB+) DAns. Electrophysiological studies of the DAns confirmed their voltage sensitivity and showed that a mutation in the PARK8 gene is associated with enhanced store-operated calcium entry. The study of high-purity DAns differentiated from the iPSCs of patients with hereditary PD using this differentiation protocol will allow for investigators to combine various research methods, from patch clamp to omics technologies, and maximize information about cell function in normal and pathological conditions.

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Section: Resultsmentioning

confidence: 99%

“…Fluorescent calcium imaging experiments were performed according to previously published protocols [ 43 , 44 ]. Briefly, DAns were loaded with 2 mM Fura-2AM in the presence of 0.025% Pluronic F-127 and incubated in the dark at room temperature for 1 h, then washed by HBSS for 20 min.…”

Section: Materials and Methodsmentioning

confidence: 99%

An Efficient 2D Protocol for Differentiation of iPSCs into Mature Postmitotic Dopaminergic Neurons: Application for Modeling Parkinson’s Disease

Lebedeva

Шарова

Grekhnev

et al. 2023

IJMS

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“…Additional experimental data obtained by using fluorescent calcium imaging (the method’s description is available in [ 20 ]) indicated that EVP4593 could not discriminate between STIM1 and STIM2 in HEK293 cells, affecting SOC in both STIM1 and STIM2 knockout cell lines ( Figure 3 ).…”

Section: The Molecular Mechanisms Of Evp4593 Activitymentioning

confidence: 99%

The Mystery of EVP4593: Perspectives of the Quinazoline-Derived Compound in the Treatment of Huntington’s Disease and Other Human Pathologies

Grekhnev

Kruchinina

Vigont

et al. 2022

IJMS

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Quinazoline derivatives have various pharmacological activities and are widely used in clinical practice. Here, we reviewed the proposed mechanisms of the physiological activity of the quinazoline derivative EVP4593 and perspectives for its clinical implication. We summarized the accumulated data about EVP4593 and focused on its activities in different models of Huntington’s disease (HD), including patient-specific iPSCs-based neurons. To make a deeper insight into its neuroprotective role in HD treatment, we discussed the ability of EVP4593 to modulate calcium signaling and reduce the level of the huntingtin protein. Moreover, we described possible protective effects of EVP4593 in other pathologies, such as oncology, cardiovascular diseases and parasite invasion. We hope that comprehensive analyses of the molecular mechanisms of EVP4593 activity will allow for the expansion of the scope of the EVP4593 application.

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1,2,3,4-dithiadiazole derivatives as a novel class of calcium signaling modulators

Novikova,

Grekhnev,

Oshkolova

et al. 2024

Biochemical and Biophysical Research Communications

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Dithiadiazole derivative 3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxide – Novel modulator of store-operated calcium entry

Cited by 5 publications

References 32 publications

An Efficient 2D Protocol for Differentiation of iPSCs into Mature Postmitotic Dopaminergic Neurons: Application for Modeling Parkinson’s Disease

An Efficient 2D Protocol for Differentiation of iPSCs into Mature Postmitotic Dopaminergic Neurons: Application for Modeling Parkinson’s Disease

The Mystery of EVP4593: Perspectives of the Quinazoline-Derived Compound in the Treatment of Huntington’s Disease and Other Human Pathologies

1,2,3,4-dithiadiazole derivatives as a novel class of calcium signaling modulators

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