Neuroprotective properties of endocannabinoids N-arachidonoyl dopamine (NADA) and N-docosahexaenoyl dopamine (DHDA) were examined in neuronal precursor cells differentiated from human induced pluripotent stem cells and subjected to oxidative stress. Both compounds exerted neuroprotective activity, which was enhanced by elevating the concentration of the endocannabinoids within the 0.1–10 μM range. However, both agents at 10 μM concentration showed a marked toxic effect resulting in death of ~30% of the cells. Finally, antagonists of cannabinoid receptors as well as the receptor of the TRPV1 endovanilloid system did not hamper the neuroprotective effects of these endocannabinoids.

This review considers different methods for obtaining induced pluripotent stem (iPS) cells and their use in biochemical and biomedical research. Some viral and nonviral methods for obtaining iPS cells are described. Basic factors involved in reprogramming are considered. It is also demonstrated that the most suitable source of iPS cells are skin fibroblasts. Properties of iPS cells and embryonic stem cells are compared, and some advantages of iPS cells for biological and biomedical investigations are emphasized. The possibilities for application of iPS cells in the development of cell models of some neurodegenerative diseases, drug screening, and cell therapy are also considered.

Development of therapeutic preparations involves several steps, starting with the synthesis of chemical compounds and testing them in different models for selecting the most effective and safest ones...

Neuroinflammation is considered to be one of the driving factors in Parkinson’s disease (PD). This study was conducted using neuronal and glial cell cultures differentiated from induced pluripotent stem cells (iPSC) of healthy donors (HD) and PD patients with different PARK2 mutations (PD). Based on the results of RNA sequencing, qPCR and ELISA, we revealed transcriptional and post-transcriptional changes in HD and PD neurons cultivated in HD and PD glial-conditioned medium. We demonstrated that if one or both of the components of the system, neurons or glia, is Parkin-deficient, the interaction resulted in the down-regulation of a number of key genes related to inflammatory intracellular pathways and negative regulation of apoptosis in neurons, which might be neuroprotective. In PD neurons, the stress-induced up-regulation of APLNR was significantly stronger compared to HD neurons and was diminished by glial soluble factors, both HD and PD. PD neurons in PD glial conditioned medium increased APLN expression and also up-regulated apelin synthesis and release into intracellular fluid, which represented another compensatory action. Overall, the reported results indicate that neuronal self-defense mechanisms contribute to cell survival, which might be characteristic of PD patients with Parkin-deficiency.

Parkinson’s disease (PD) is the most serious movement disorder, but the actual cause of this disease is still unknown. Induced pluripotent stem cell-derived neural cultures from PD patients carry the potential for experimental modeling of underlying molecular events. We analyzed the RNA-seq data of iPSC-derived neural precursor cells (NPCs) and terminally differentiated neurons (TDNs) from healthy donors (HD) and PD patients with mutations in PARK2 published previously. The high level of transcription of HOX family protein-coding genes and lncRNA transcribed from the HOX clusters was revealed in the neural cultures from PD patients, while in HD NPCs and TDNs, the majority of these genes were not expressed or slightly transcribed. The results of this analysis were generally confirmed by qPCR. The HOX paralogs in the 3′ clusters were activated more strongly than the genes of the 5′ cluster. The abnormal activation of the HOX gene program upon neuronal differentiation in the cells of PD patients raises the possibility that the abnormal expression of these key regulators of neuronal development impacts PD pathology. Further research is needed to investigate this hypothesis.

—The technology for producing human induced pluripotent stem cells (iPSCs) and the possibility of directed differentiation into specialized cells of all body tissues have opened unique opportunities for studying the molecular genetic basis of the pathogenesis of neurodegenerative diseases in vitro and effective screening for compounds with neuroprotective activity. The aim of this work was to obtain glial cell cultures from iPSCs of a healthy donor and a patient with the familial form of Parkinson’s disease (G2019S mutation in the LRRK2) and to characterize them. At the first stage, we compared the three previously described protocols for the differentiation of glial cells from neural precursors of human iPSCs and selected the method most acceptable under our conditions in terms of the quality and time necessary for obtaining the desired cultures. Glial cell cultures obtained by this method were characterized by the levels of expression of a number of neuroglial differentiation genes. Also, in the resulting cultures, we analyzed the expression of genes of some neurotrophic factors (GDNF, BDNF, NGF, NT3). It was shown that the culture medium conditioned by glial cells from a patient with Parkinson’s disease had a negative effect on the growth of neurites of dopaminergic neurons in differentiated cultures of a healthy donor, decreasing their length by a factor of 2.