Arthrogryposis, which represents a group of congenital disorders, includes various forms. One such form is amyoplasia, which most commonly presents in a sporadic form in addition to distal forms, among which hereditary cases may occur. This condition is characterized by limited joint mobility and muscle weakness, leading to limb deformities and various clinical manifestations. At present, the pathogenesis of this disease is not clearly understood, and its diagnosis is often complicated due to significant phenotypic diversity, which can result in delayed detection and, consequently, limited options for symptomatic treatment. In this study, a transcriptomic analysis of the affected muscles from patients diagnosed with amyoplasia was performed, and more than 2000 differentially expressed genes (DEGs) were identified. A functional analysis revealed disrupted biological processes, such as vacuole organization, cellular and aerobic respiration, regulation of mitochondrion organization, cellular adhesion, ATP synthesis, and others. The search for key nodes (hubs) in protein-protein interaction networks allowed for the identification of genes involved in mitochondrial processes.

Bruck syndrome is a rare autosomal recessive disorder characterized by increased bone fragility and joint contractures similar to those in arthrogryposis and is known to be associated with mutations in the FKBP10 (FKBP prolyl isomerase 10) and PLOD2 (Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2) genes. These genes encode endoplasmic reticulum proteins that play an important role in the biosynthesis of type I collagen, which in turn affects the structure and strength of connective tissues and bones in the body. Mutations are associated with disturbances in both the primary collagen chain and its post-translational formation, but the mechanism by which mutations lead to Bruck syndrome phenotypes has not been determined, not only because of the small number of patients who come to the attention of researchers but also because of the lack of disease models. In our work, we investigated the cellular effects of two forms of the wild-type PLOD2 gene, as well as the PLOD2 gene with homozygous mutation c.1885A>G (p.Thr629Ala). The synthesized genetic constructs were transfected into HEK293 cell line and human skin fibroblasts (DF2 line). The localization of PLOD2 protein in cells and the effects caused by the expression of different isoforms—long, short, and long with mutation—were analyzed. In addition, the results of the transcriptome analysis of a patient with Bruck syndrome, in whom this mutation was detected, are presented.

Kombucha tea was made by the fermentation of SCOBY culture of green tea broth with the addition of Fucus vesiculosus algae extract, Cetraria islandica lichen extract and their mixture. Kombucha was also made without the herbal supplements as a control. After 11 days of fermentation, in addition to the yeast Brettanomyces bruxellensis and the bacteria Komagataeibacter rhaeticus and Komagataeibacter hansenii contained in all of the samples, the yeast Zygosaccharomyces bailii and bacteria Komagataeibacter cocois were detected in the samples with the herbal extracts. In all of the kombucha with herbal additives, the total fraction of yeast was decreased as compared to the control. The total content of polyphenols and the antioxidant activity of the beverages with and without the addition of herbal extracts were comparable. The kombucha made with the algae extract showed an increased content of sucrose and organic acids, while the fructose and glucose content in the samples with algae and the mixture of extracts were lower than in the other samples. The samples with the algae extract had the highest organoleptic indicators "aroma", "clarity" and "acidity", while the control samples had slightly higher indicators of "taste" and "aftertaste". The results of this study indicate the potential of algae and lichens as functional supplements for obtaining non-alcoholic fermented beverages with additional nutraceutical value.

Huntington's disease (HD) is one of the human neurodegenerative diseases for which there is no effective treatment. Therefore, there is a strong demand for a novel neuroprotective agent that can alleviate its course. Fullerene derivatives are considered to be such agents; however, they need to be comprehensively investigated in model organisms. In this work, neuroprotective activity of C60(OH)30 and C120O(OH)44 fullerenols was analyzed for the first time in a Drosophila transgenic model of HD. Lifespan, behavior, oxidative stress level and age-related neurodegeneration were assessed in flies with the pathogenic Huntingtin protein expression in nerve cells. Feed supplementation with hydroxylated C60 fullerene and C120O dimer oxide molecules was shown to diminish the oxidative stress level and neurodegenerative processes in the flies' brains. Thus, fullerenes displayed neuroprotective activity in this model.

Parkinson's disease (PD) is a neurodegenerative disease characterised by the formation of Lewy bodies and progressive loss of dopaminergic (DA) neurons in the substantia nigra. Lewy bodies mainly consist of alpha-synuclein, which plays a critical role in the pathophysiology of PD. The alpha-synuclein is encoded by the SNCA gene and is the first identified gene associated with hereditary PD. Currently, there are at least six disease-associated mutations in alpha-synuclein that cause dominantly inherited familial forms of PD. Targeted expression of human SNCA.WT/SNCA.A30P/SNCA.A53T gene in Drosophila melanogaster over specific times employing a temperature-dependent UAS/GAL4 - GAL80 system allows for the evaluation of neurodegenerative processes. In this study, SNCA was expressed only in the adult stage of Drosophila development for 1 or 2 weeks, followed by repression of gene expression for the rest of the fly's life. It was demonstrated that the level of pathology significantly depends on the duration of alpha-synuclein expression. SNCA gene expression over a longer period of time caused the death of DA neurons, decreased levels of dopamine and locomotor ability. In this case, the observed neurodegenerative processes correlated with the accumulation of alpha-synuclein in the Drosophila brain. Importantly, repression of alpha-synuclein expression led to elimination of the soluble protein fraction, in contrast to the insoluble fraction. No further significant development of characteristic signs of pathology was observed after the alpha-synuclein expression was blocked. Thus, we suggest that reduction of alpha-synuclein expression alone contributes to slowing down the development of PD-like symptoms.

Various neurodegenerative disorders are associated with human NTE/PNPLA6 dysfunction. Mechanisms of neuropathogenesis in these diseases are far from clearly elucidated. Hereditary spastic paraplegia belongs to a type of neurodegeneration associated with NTE/PNLPLA6 and is implicated in neuron death. In this study, we used Drosophila melanogaster to investigate the consequences of neuronal knockdown of swiss cheese (sws)—the evolutionarily conserved ortholog of human NTE/PNPLA6—in vivo. Adult flies with the knockdown show longevity decline, locomotor and memory deficits, severe neurodegeneration progression in the brain, reactive oxygen species level acceleration, mitochondria abnormalities and lipid droplet accumulation. Our results suggest that SWS/NTE/PNPLA6 dysfunction in neurons induces oxidative stress and lipid metabolism alterations, involving mitochondria dynamics and lipid droplet turnover in neurodegeneration pathogenesis. We propose that there is a complex mechanism in neurological diseases such as hereditary spastic paraplegia, which includes a stress reaction, engaging mitochondria, lipid droplets and endoplasmic reticulum interplay.

Glia are crucial for the normal development and functioning of the nervous system in many animals. Insects are widely used for studies of glia genetics and physiology. Drosophila melanogaster surface glia (perineurial and subperineurial) form a blood–brain barrier in the central nervous system and blood–nerve barrier in the peripheral nervous system. Under the subperineurial glia layer, in the cortical region of the central nervous system, cortex glia encapsulate neuronal cell bodies, whilst in the peripheral nervous system, wrapping glia ensheath axons of peripheral nerves. Here, we show that the expression of the evolutionarily conserved swiss cheese gene is important in several types of glia. swiss cheese knockdown in subperineurial glia leads to morphological abnormalities of these cells. We found that the number of subperineurial glia nuclei is reduced under swiss cheese knockdown, possibly due to apoptosis. In addition, the downregulation of swiss cheese in wrapping glia causes a loss of its integrity. We reveal transcriptome changes under swiss cheese knockdown in subperineurial glia and in cortex + wrapping glia and show that the downregulation of swiss cheese in these types of glia provokes reactive oxygen species acceleration. These results are accompanied by a decline in animal mobility measured by the negative geotaxis performance assay.

An urgent task of modern medicine is the search for drugs that can stop or slow down the course of neurodegenerative diseases, in particular Alzheimer's disease. The aim of this work was to determine the effect of fullerenol C-60(OH)(30) on the pathogenesis of Alzheimer's disease in the Drosophila melanogaster model. The effect of fullerenol on the life expectancy, the level of geotaxis, learning and memory, and the levels of neurodegeneration and reactive oxygen species in the animal brain was studied. Based on the results, it can be assumed that fullerenol C-60(OH)(30) is a promising agent for the development of complex therapy for Alzheimer's disease.

Глиальные клетки (ГК) являются наиболее распространенным типом клеток в центральной нервной системе. Интерес к ним значительно увеличился за последние десятилетия по мере осознания того, что глия является не только «опорными» клетками для нейронов, но также регулирует важные аспекты развития и функционирования нервной системы. У позвоночных ГК выполняют опорную, трофическую, секреторную, разграничительную и защитную функции. Несмотря на то, что нервная система Drosophila melanogaster относительно проста по своей структуре, ей присущи характеристики сложно устроенной глии млекопитающих. Схожесть глии Drosophila melanogaster и млекопитающих на молекулярном и морфологическом уровне дает возможность предположить, что исследование глии беспозвоночных позволит лучше понять основные вопросы развития глии у млекопитающих. Использование Drosophila melanogaster дает возможность изучать различные нейрон-глиальные взаимодействия в интактном организме, а использование широкого набора молекулярно-генетических методов позволяет исследовать фундаментальные вопросы природы глии. В обзоре дана классификация глиальных клеток Drosophila melanogaster, описаны известные на сегодняшний день функции всех типов глии насекомого, а также проведено сравнение функций разных типов глиальных клеток млекопитающих и дрозофилы.

Обоснование. Врожденные контрактуры — это гетерогенная группа заболеваний. Они характеризуются различным прогнозом для пациента, и для их лечения применяют разные методы. Клиническое наблюдение. В статье описан семейный случай наследственной сенсорно-моторной полинейропатии, обусловленной мутацией с.943G>A (р.Arg315Trp) в гене TRPV4 (transient receptor potential vanilloid cation channel 4, NM_021625.4). Представлены клинико-неврологическая характеристика пациента, результаты генетического и нейрофизиологического исследования. Обсуждение. Наиболее часто мутации в гене TRPV4 приводят к трем основным заболеваниям: наследственной аутосомно-доминантной сенсомоторной нейропатии, тип 2С; скапулоперонеальной спинальной мышечной атрофии; врожденной непрогрессирующей дистальной спинальной мышечной атрофии с контрактурами. В статье подробно описана дифференциальная диагностика наследственной сенсомоторной полинейропатии, позволяющая практикующим врачам правильно верифицировать заболевание. Заключение. Пациенты с врожденными множественными контрактурами нуждаются в наблюдении и ортопедов, и неврологов с включением в план обследования таких методов, как нейрофизиологический и генетический, что позволяет верифицировать заболевание, оптимизировать тактику лечения, а также прогнозировать его результаты.

Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease.