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Filamin C (FLNC) is a member of a high-molecular weight protein family, which bind actin filaments in the cytoskeleton of various cells. In human genome FLNC is encoded by the FLNC gene located on chromosome 7 and is expressed predominantly in striated skeletal and cardiac muscle cells. Filamin C is involved in organization and stabilization of thin actin filaments three-dimensional network in sarcomeres, and is supposed to play a role of mechanosensor transferring mechanical signals to different protein targets. Under mechanical stress FLNC can undergo unfolding that increases the risk of its aggregation. FLNC molecules with an impaired native structure could be eliminated by the BAG3-mediated chaperone-assisted selective autophagy. Mutations in the FLNC gene could be accompanied by the changes in FLNC interaction with its protein partners and could lead to formation of aggregates, which overload the autophagy and proteasome protein degradation systems, thus facilitating development of various pathological processes. Molecular mechanisms of the FLNC -associated congenital disorders, called filaminopathies, remain poorly understood. This review is devoted to analysis of the structure and mechanisms of filamin C function in muscle and heart cells in normal state and in the FLNC -associated pathologies. The presented data summarize the results of research at the molecular, cellular, and tissue levels and allow us to outline promising ways for further investigation of pathogenetic mechanisms in filaminopathies.

Organoids are three-dimensional (3D) cell cultures that replicate some of the key features of morphology, spatial architecture, and functions of a particular organ. Organoids can be generated from both adult and pluripotent stem cells (PSCs), and complex organoids can also be obtained by combining different types of cells, including differentiated cells. The ability of pluripotent cells to self-organize into organotypic structures containing several cell subtypes specific for a particular organ was used for creating organoids of the brain, eye, kidney, intestine, and other organs. Despite the advantages of using PSCs for obtaining organoids, an essential shortcoming that prevents their widespread use has been a low yield when they are obtained from a PSC monolayer culture and a large variation in size. This leads to great heterogeneity on further differentiation. In this article, we describe our own protocol for generating standardized organoids, with emphasis on a method for generating brain organoids, which allows scaling-up experiments and makes their cultivation less expensive and easier.

Studying pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD), requires adequate disease models. The available patient's material is limited to biological fluids and post mortem brain samples. Disease modeling and drug screening can be done in animal models, although this approach has its own limitations, since laboratory animals do not suffer from many neurodegenerative diseases, including PD. The use of neurons obtained by targeted differentiation from induced pluripotent stem cells (iPSCs) with known genetic mutations, as well as from carriers of sporadic forms of the disease, will allow to elucidate new components of the molecular mechanisms of neurodegeneration. Such neuronal cultures can also serve as unique models for testing neuroprotective compounds and monitoring neurodegenerative changes against a background of various therapeutic interventions. In the future, dopaminergic neurons differentiated from iPSCs can be used for cell therapy of PD.