A5043997109- Lysosomal Storage Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Cellular transport and secretion
- Nuclear Receptors and Signaling
- Trypanosoma species research and implications
- Neurogenetic and Muscular Disorders Research
- Erythrocyte Function and Pathophysiology
- COVID-19 Clinical Research Studies
- RNA Interference and Gene Delivery
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
- Autophagy in Disease and Therapy
- Calcium signaling and nucleotide metabolism
- Sphingolipid Metabolism and Signaling
- Pancreatic function and diabetes
- Nonlinear Dynamics and Pattern Formation
- Alzheimer's disease research and treatments
- Extracellular vesicles in disease
- Adipokines, Inflammation, and Metabolic Diseases
- Carbohydrate Chemistry and Synthesis
- Inflammasome and immune disorders
- Adenosine and Purinergic Signaling
- SARS-CoV-2 and COVID-19 Research
- Macrophage Migration Inhibitory Factor
- Biomedical Research and Pathophysiology
Petersburg Nuclear Physics Institute
2020-2025
First Pavlov State Medical University of St. Petersburg
2023-2025
Kurchatov Institute
2020-2024
Background: Mutations in the glucocerebrosidase (GBA1) and leucine-rich repeat kinase 2 (LRRK2) genes, encoding lysosomal enzyme (GCase) (LRRK2), respectively, are most common related to Parkinson's disease (PD). Recent data suggest a possible functional interaction between GCase LRRK2 their involvement sphingolipid metabolism. The aim of present study was describe clinical course evaluate activities concentrations blood patients with PD associated dual mutations p.N370S GBA1 p.G2019S...
Recent data described that patients with lysosomal storage disorders (LSDs) may have clinical schizophrenia (SCZ) features. Disruption of lipid metabolism in SCZ pathogenesis was found. Clinical features been demonstrated several (LSDs). Taking into account the critical role function for neuronal cells’ dysfunction could be proposed pathogenesis. The current study analyzed enzyme activities and alpha-synuclein level blood late-onset SCZ. In total, 52 SCZ, 180 sporadic Parkinson’s disease...
Mutations in the GBA1 gene represent major genetic risk factor for Parkinson’s disease (PD). The lysosomal enzyme beta-glucocerebrosidase (GCase) encoded by participates both endolysosomal pathway and immune response. Disruption of these mechanisms is involved PD pathogenesis. However, molecular associated with mutations (GBA-PD) are unknown today particular due to partial penetrance variants PD. modifiers have not been elucidated. We characterized transcriptomic profiles cells from...
Mutations of the GBA gene, encoding for lysosomal enzyme glucocerebrosidase (GCase), are greatest genetic risk factor Parkinson’s disease (PD) with frequency between 5% and 20% across world. N370S L444P two most common mutations in gene. PD carriers severe mutation gene is characterized by earlier age at onset compared to N370S. Not every carrier develop during one’s lifetime. In current study we aimed find expression signatures associated (GBA-PD) using RNA-seq. We transcriptome...
Transcriptomic analysis conducted by us previously revealed upregulation of genes involved in low-density lipoprotein particle receptor (LDLR) activity pathway lethal COVID-19 caused SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2). Last data suggested the possible role extracellular vesicles pathogenesis. The aim present study was to retrospectively evaluate parameters cholesterol metabolism and newly identified EVs, exomeres, as predictors fatal outcome patients infected...
Last data described that patients with lysosomal storage disorders (LSDs) may have clinical schizophrenia (SCZ). The dysfunction in SCZ pathogenesis, particularly, due to the critical role of function for neuronal cells could be proposed. current study focused on estimation enzyme activities and alpha-synuclein level blood late-onset SCZ. 52 SCZ, 180 sporadic Parkinson’s disease (sPD) patients, 176 controls were recruited. enzymatic activity enzymes associated mucopolysaccharidosis...
Abstract To date, the molecular mechanisms of common neurodegenerative disorder Parkinson’s disease (PD) are unknown and, as a result, there is no neuroprotective therapy that may stop or slow down process neuronal cell death. The aim current study was to evaluate prospects using mTOR molecule potential target for PD due dose-dependent effect kinase activity inhibition on cellular parameters associated with, pathogenesis. used peripheral blood monocyte-derived macrophages and SH-SY5Y...
Introduction. Mutations in a GBA1 gene, which encodes lysosomal enzyme called glucocerebrosidase (GCase), are the most common genetic risk factor for Parkinson's disease (PD). The pathogenesis of PD results from death dopaminergic neurons substantia nigra brain, is associated with aggregation α-synuclein protein. However, not all mutation carriers develop during their lifetime. aim this study was to evaluate GCase activity and levels CD45+ blood cells patients mutations (GBА1-PD),...
To date, the molecular mechanisms of common neurodegenerative disorder Parkinson’s disease (PD) are unknown and, as a result, there is no neuroprotective therapy that may stop or slow down process neuronal cell death. The aim current study was to evaluate prospects using mTOR molecule potential target for PD due dose-dependent effect kinase activity inhibition on cellular parameters, alteration which associated with pathogenesis PD. performed peripheral blood monocyte-derived macrophages and...
The molecular mechanisms of the neurodegenerative disorder Parkinson’s disease (PD) associated with mutations in GBA1 gene which encodes lysosomal enzyme glucocerebrosidase (GCase) gene, (GBA1-PD) are unknown. Transcriptome analysis cellular and animal models induced parkinsonism GCase dysfunction, followed by subsequent validation, showed impairment mTOR-dependent autophagy. potential therapeutic significance mTOR for treatment GBA1-PD was also assessed.
The molecular mechanisms of synucleinopathies are unknown; as a result, there no biomarkers or neuroprotective therapies. Previous studies have shown that characterized by activity lysosomal hydrolases activity, and kinase LRRK2 affects activity. In this study, we propose biomarker for the differential diagnosis evaluate potential use an inhibitor their treatment.
Abstract Transcriptomic analysis conducted by us previously revealed upregulation of genes involved in low-density lipoprotein particle receptor (LDLR) activity pathway lethal COVID-19. Last data suggested the possible role extracellular vesicles and exomeres COVID-19 pathogenesis. The aim present study was to retrospectively evaluate parameters cholesterol metabolism as predictors fatal outcome Blood from 39 patients with severe (the main cohort) were collected at time admission intensive...
Introduction. In carriers of a mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene, risk Parkinson disease (PD) is increased by 78 times. However, not all GBA gene mutations develop PD during their lifetime. We hypothesize that dysfunction membrane proteins involved autophagy and transport into lysosomes can contribute to development gene. The aim study was assess contribution LAMP2 SCARB2 genes expression CD45+ peripheral blood cells GBA-PD. Materials methods. examined 9 patients...
The prospect of using LRRK2 inhibitors as treatment strategy for Parkinson’s disease (PD) associated with mutations in the gene GBA1 (GBA-PD), encoding lysosomal enzyme glucocerebrosidase (GCase) is currently being discussed. We assessed effectiveness kinase activity inhibitor MLi-2 restoring GCase functions and effect on other enzymes cell lines patients GBA-PD, LRRK2-PD.
The molecular mechanisms of the neurodegenerative disease, Parkinson’s disease (PD), associated with mutations in GBA1 gene (GBA-PD) are unknown. Recent data point to role autophagy, particular PI3K/AKT/mTOR pathway, PD pathogenesis. study revealed pronounced alterations expression autophagy-related genes involved pathway GBA-PD. v
Mutations in the glucocerebrosidase gene (GBA1), which encodes lysosomal enzyme (GCase), can cause Gaucher disease, an autosomal recessive and increase risk of Parkinson’s disease (PD). The developing PD for carriers homozygous heterozygous GBA1 mutations increases by 8–10 times, but not all develop during their lifetime. Additionally, GBA-associated (GBA-PD) represents 10 to 30% forms parkinsonism. development mechanism GBA-PD remains unknown. A decrease GCase activity accumulation...