Publications by authors named "Elena V Kaznacheyeva"
The incidence and development of cancer are highly dependent on pathological disturbances in calcium homeostasis of the cell. One of the major pathways for calcium entry is store-operated calcium entry (SOCE), which functions in virtually all cell types. Changes in the expression level of the main proteins organizing SOCE are observed during the development of various cancer types, particularly breast cancer (BC).
View Article and Find Full Text PDFArticle Synopsis
- * The study investigated calcium signaling in GABA-ergic medium spiny neurons derived from iPSCs created through different methods (lentivirus and Sendai virus) from the same donor's fibroblasts.
- * Results showed no significant differences in calcium signaling between neurons from both reprogramming methods, indicating compatibility for combining data from different iPSC models and enhancing biobanking potential.
Article Synopsis
- * Researchers discovered that a specific compound, 3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxide, significantly reduces calcium uptake by affecting store-operated calcium (SOC) channels, establishing a new class of inhibitors.
- * The study compared different derivatives of 1,2,3,4-dithiadiazoles, finding that two specific compounds were particularly effective at reducing SOC entry, highlighting the role of certain chemical substituents in enhancing their inhibitory effects.
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.
View Article and Find Full Text PDFArticle Synopsis
- Quinazoline derivatives, like EVP4593, are known for their various pharmacological activities and show promise in clinical use.
- The review highlights EVP4593's neuroprotective effects in Huntington's disease (HD) through its modulation of calcium signaling and reduction of the huntingtin protein levels, especially in patient-specific neurons.
- Additionally, the text discusses the potential protective benefits of EVP4593 in other diseases, including cancer, heart disease, and infections, suggesting it could have a broader clinical application.
Pathological calcium homeostasis accompanies the development of a large number of different diseases, therefore, the search for new modulators of calcium signaling remains highly actual. Last decades store-operated calcium channels have been repeatedly postulated as a therapeutic target, so the compounds acting on them can be considered promising drug prototypes. Here, we tested several derivatives of 1,2,3,4-dithiadiazole, 1,3-thiazine, pyrazolopyrimidine and thiohydrazides for the ability to affect the thapsigargin-induced calcium response.
View Article and Find Full Text PDFArticle Synopsis
- - The development of cell reprogramming technologies, particularly iPSCs, has revolutionized the study of human diseases, especially neurodegenerative disorders, by offering new models for both hereditary and sporadic cases.
- - iPSCs allow researchers to examine the specific cells affected by these diseases, helping to uncover the molecular mechanisms of neurodegeneration and aiding in the identification of effective treatments.
- - This review specifically highlights how altered calcium signaling, a crucial intracellular pathway, is observed in various neurodegenerative diseases using iPSCs-based models.
Impairment of proteostasis network is one of the characteristic features of many age-related neurodegenerative disorders including autosomal dominantly inherited Huntington's disease (HD). In HD, N-terminal portion of mutant huntingtin protein containing expanded polyglutamine repeats accumulates as inclusion bodies and leads to progressive deterioration of various cellular functioning including proteostasis network. Here we report that Withaferin A (a small bioactive molecule derived from Indian medicinal plant, Withania somnifera) partially rescues defective proteostasis by activating heat shock response (HSR) and delays the disease progression in a HD mouse model.
View Article and Find Full Text PDFArticle Synopsis
- * Research using induced pluripotent stem cell technology revealed that HD76 neurons experience abnormal calcium signaling, showing increased calcium uptake that does not correlate with the length of the mutant huntingtin gene's polyglutamine tract.
- * The study identified high levels of the protein STIM2, which is linked to excessive calcium entry in HD neurons, and found that the drug EVP4593 can reduce levels of both huntingtin and STIM2, highlighting STIM2 as a potential target for developing new treatments for HD
Huntington's disease (HD) is a hereditary neurodegenerative disease that is caused by polyglutamine expansion within the huntingtin (HTT) gene. One of the cellular activities that is dysregulated in HD is store-operated calcium entry (SOCE), a process by which Ca release from the endoplasmic reticulum (ER) induces Ca influx from the extracellular space. HTT-associated protein-1 (HAP1) is a binding partner of HTT.
View Article and Find Full Text PDFBackground: Huntington's disease (HD) is an incurable hereditary neurodegenerative disorder, which manifests itself as a loss of GABAergic medium spiny (GABA MS) neurons in the striatum and caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. There is no cure for HD, existing pharmaceutical can only relieve its symptoms.
Results: Here, induced pluripotent stem cells were established from patients with low CAG repeat expansion in the huntingtin gene, and were then efficiently differentiated into GABA MS-like neurons (GMSLNs) under defined culture conditions.
Polyglutamine diseases are a group of pathologies affecting different parts of the brain and causing dysfunction and atrophy of certain neural cell populations. These diseases stem from mutations in various cellular genes that result in the synthesis of proteins with extended polyglutamine tracts. In particular, this concerns huntingtin, ataxins, and androgen receptor.
View Article and Find Full Text PDF