Human induced pluripotent stem (iPS) cells have the potential to give rise to a new era in Parkinson’s disease (PD) research. As a unique source of midbrain dopaminergic (DA) neurons, iPS cells provide unparalleled capabilities for investigating the pathogenesis of PD, the development of novel anti-parkinsonian drugs, and personalized therapy design. Significant progress in developmental biology of midbrain DA neurons laid the foundation for their efficient derivation from iPS cells. The introduction of 3D culture methods to mimic the brain microenvironment further expanded the vast opportunities of iPS cell-based research of the neurodegenerative diseases. However, while the benefits for basic and applied studies provided by iPS cells receive widespread coverage in the current literature, the drawbacks of this model in its current state, and in particular, the aspects of differentiation protocols requiring further refinement are commonly overlooked. This review summarizes the recent data on general and subtype-specific features of midbrain DA neurons and their development. Here, we review the current protocols for derivation of DA neurons from human iPS cells and outline their general weak spots. The associated gaps in the contemporary knowledge are considered and the possible directions for future research that may assist in improving the differentiation conditions and increase the efficiency of using iPS cell-derived neurons for PD drug development are discussed.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetrical joint inflammation, cartilage degradation, and bone erosion. This review explores the multifaceted aspects of RA pathogenesis, focusing on the dynamic interplay between innate and adaptive immune responses, genetic predisposition, and environmental triggers. The development of RA involves genetic susceptibility and trigger events such as infections, trauma, smoking, obesity, and microbiome alterations, fostering autoimmune reactions and tissue/organ destruction. The innate immune response, including toll-like receptor activation and synovial fibroblasts’ roles, contributes to the acceleration of inflammatory processes in joint tissues. Monocytes and macrophages organize and sustain chronic joint inflammation, leading to tissue damage and bone resorption, while highlighting the significance of CD14 and CD16 subsets in RA pathogenesis. In the adaptive immune response, aberrant activation and proliferation of CD4+ T cells and the role of regulatory T cells in maintaining immune tolerance are discussed. Target cytokines like TNF-α, IL-6, IL-1, IL-17, and BAFF, as well as chemokines such as CCL2, CXCL10, CCL5, and CXCL12, have emerged as critical components in managing chronic inflammation and joint damage in RA. This comprehensive overview provides insights into the pathophysiology of RA and potential therapeutic avenues, emphasizing the importance of understanding these complex immunological and genetic mechanisms for developing more effective treatment strategies.

Oxidative stress (OS) is implicated in the pathogenesis of several neurodegenerative diseases. We have previously shown that N-acyl dopamines (N-ADA and N-DDA) protect the neural cells of healthy donors and patients with Parkinson’s disease from OS. In this study, we assessed the effects of N-acyl dopamines on the expression of neurotrophic factors in human-induced pluripotent stem cell-derived neuronal cultures enriched with dopaminergic neurons under conditions of OS induced by hydrogen peroxide. We showed that hydrogen peroxide treatment increased BDNF but not GDNF mRNA levels, while it did not affect the secretion of corresponding proteins into the culture medium of these cells. Application of N-acyl dopamines promoted BDNF release into the culture medium. Under conditions of OS, N-DDA also increased TRKB, TRKC and RET mRNA levels. Furthermore, N-acyl dopamines prevented cell death 24 h after OS induction and promoted the expression of antioxidant enzymes GPX1, GPX7, SOD1, SOD2 and CAT, as well as reduced the BAX/BCL2 mRNA ratio. These findings indicate that stimulation of the expression of neurotrophic factors and their receptors may underlie the neuroprotective effects of N-acyl dopamines in human neurons.