A5001684239- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Neurological disorders and treatments
- Nuclear Receptors and Signaling
- Amyotrophic Lateral Sclerosis Research
- Cholinesterase and Neurodegenerative Diseases
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- Neuroscience and Neuropharmacology Research
- Histone Deacetylase Inhibitors Research
- Alcoholism and Thiamine Deficiency
- Effects of Radiation Exposure
- Cardiomyopathy and Myosin Studies
- Biochemical effects in animals
- Functional Brain Connectivity Studies
- Biochemical Acid Research Studies
- Diet and metabolism studies
- Ginkgo biloba and Cashew Applications
- Prion Diseases and Protein Misfolding
- Phytochemistry and Bioactivity Studies
- Lanthanide and Transition Metal Complexes
- Radiation Therapy and Dosimetry
- Lysosomal Storage Disorders Research
- Prenatal Substance Exposure Effects
Institute of Physiologically Active Compounds
2019-2025
Nazarbayev University
2025
Cardiff University
2019-2024
Belgorod National Research University
2021-2023
Sechenov University
2023
Institute of Problems of Chemical Physics
2022
Background: The inheritance of the short SLC6A4 allele, encoding serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging female sex further exacerbating these conditions. Both central peripheral mechanisms compromised (5-HT) system play crucial roles this context. Previous studies on SERT-deficient (Sert-/-) mice, which model human SERT deficiency, have demonstrated emotional disturbances, exacerbated by exposure a high-fat...
Parkinson's disease is the second most common neurodegenerative disease. Unfortunately, there still no definitive disease-modifying therapy. In our work, antiparkinsonian potential of trans-epoxide (1S,2S,3R,4S,6R)-1-methyl-4-(prop-1-en-2-yl)-7-oxabicyclo [4.1.0]heptan-2,3-diol (E-diol) was analyzed in a rotenone-induced neurotoxicity model using vitro, vivo and ex approaches. It conducted as part study mitoprotective properties compound. E-diol has been shown to have cytoprotective SH-SY5Y...
The etiology and pathogenesis of Parkinson's disease (PD) are tightly linked to the gain-of-function α-synuclein. However, gradual accumulation α-synuclein aggregates in dopaminergic neurons substantia nigra pars compacta (SNpc) leads depletion functional pool soluble α-synuclein, therefore, creates loss-of-function conditions, particularly presynaptic terminals these neurons. Studies how this late-onset a protein involved many important steps neurotransmission contributes PD progression...
In vitro/in vivo detection of copper ions is a challenging task but one which important in the development new approaches to diagnosis and treatment cancer hereditary diseases such as Alzheimer's, Wilson's, etc. this paper, we present nanopipette sensor capable measuring Cu
Abstract Dysfunction of the RNA-binding protein (RBP) FUS implicated in RNA metabolism can cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Mutations affecting nuclear localization drive splicing defects stimulate formation non-amyloid inclusions affected neurons. However, mechanism by which mutations contribute to development ALS remains uncertain. Here we describe a pattern changes dynamics continuous proteinopathy induced mislocalized FUS. We show that...
Synucleins, a family of three proteins highly expressed in neurons, are predominantly known for the direct involvement α-synuclein etiology and pathogenesis Parkinson's certain other neurodegenerative diseases, but their precise physiological functions still not fully understood. Previous studies have demonstrated importance as modulator various mechanisms implicated chemical neurotransmission, information concerning synuclein members, β-synuclein γ-synuclein, molecular processes within...
Novel monoterpene-based hydroxamic acids of two structural types were synthesized for the first time. The type consisted compounds with a hydroxamate group directly bound to acyclic, monocyclic and bicyclic monoterpene scaffolds. second included connected moiety through aliphatic (hexa/heptamethylene) or aromatic linkers. An in vitro analysis biological activity demonstrated that some these molecules had powerful HDAC6 inhibitory activity, presence linker area structure playing key role. In...
Abstract Multiple clinical and experimental evidences suggest that amyotrophic lateral sclerosis (ALS) frontotemporal lobar degeneration (FTLD) are members of a disease continuum. Pathological inclusions fused in sarcoma (FUS) protein have been observed subsets patients with these diseases but their anatomical distribution is different for two diseases. These structures present motor neurons ALS cases cortical FTLD cases. Expression C‐terminally truncated form human FUS causes an early onset...
The malfunctioning of the brain synucleins is associated with pathogenesis Parkinson’s disease. Synucleins’ ability to modulate various pre-synaptic processes suggests their modifying effects on electroencephalogram (EEG) recorded from different structures. Disturbances in interrelations between them are critical for onset and evolution neurodegenerative diseases. Recently, we have shown that, mice lacking several synucleins, differences frequency spectra EEG structures correlated...
In orbital and ground-based experiments, it has been demonstrated that ionizing radiation (IR) can stimulate the locomotor exploratory activity of rodents, but underlying mechanism this phenomenon remains undisclosed. Here, we studied effect combined IR (0.4 Gy γ-rays 0.14 carbon-12 nuclei) on rats, assessed sensorimotor cortex volume by magnetic resonance imaging-based morphometry at 1 week 7 months post-irradiation. The tissues were processed to determine whether behavioral morphologic...
Abstract Previous studies of the alpha-synuclein null mutant mice on C57Bl6 genetic background have revealed reduced number dopaminergic neurons in their substantia nigra pars compacta (SNpc). However, presence genomes studied mouse lines additional modifications that affect expression genes located a close proximity to alpha-synuclein-encoding Snca gene makes these data open various interpretations. To unambiguously demonstrate absence is primary cause observed deficit neurons, we employed...
Mutations in the gene encoding RNA/DNA-binding protein Fused Sarcoma (FUS) have been detected familial amyotrophic lateral sclerosis (ALS) patients.FUS has found to be a critical component of oxidative damage repair complex that might explain its role neurodegeneration.Here, we examined what impact antioxidant treatment with thiamine (vitamine B1), or more bioavailable derivative O,Sdibenzoylthiamine (DBT), would on hallmarks pathology FUS[1-359]-transgenic mouse model ALS.From 8-weeks old,...
Evident similarities in pathological features aging and Alzheimer's disease (AD) raise the question of a role for natural age-related adaptive mechanisms prevention/elimination disturbances interrelations between different brain areas. In our previous electroencephalogram (EEG) studies on 5xFAD- FUS-transgenic mice, as models AD amyotrophic lateral sclerosis (ALS), this suggestion was indirectly confirmed. current study, changes direct EEG synchrony/coherence structures were evaluated.In...
CNS inflammation, including microglial activation, in response to peripheral infections are known contribute the pathology of both familial and sporadic neurodegenerative disease. The relationship between Fused-in-Sarcoma Protein (FUS)-mediated disease transgenic FUS[1–359] animals systemic inflammatory have not been explored. Here, we investigated gene expression behavioural responses lipopolysaccharide-induced (LPS; 0.1 mg/kg) inflammation mice. these mice recapitulates key features mutant...
Abstract Aims To assess effects of DF402, a bioisostere Dimebon/Latrepirdine, on the disease progression in transgenic model amyotrophic lateral sclerosis (ALS) caused by expression pathogenic truncated form human FUS protein. Methods Mice received DF402 from age 42 days and onset clinical signs, duration animal lifespan were monitored for experimental control animals, multiple parameters their gait assessed throughout pre‐symptomatic stage using CatWalk system followed bioinformatic...
Maternal alcohol consumption is one of the strong predictive factors use and consequent abuse; however, investigations sex differences in response to prenatal exposure (PAE) are limited. Here we compared effects PAE throughout gestation on preference, state anxiety mRNA expression presynaptic proteins α-, β- γ-synucleins brain adult (PND60) male female Wistar rats. Total RNA was isolated from hippocampus, midbrain hypothalamus levels were assessed with quantitative RT-PCR. Compared naïve...
Synucleins comprise a family of small proteins highly expressed in the nervous system vertebrates and involved various intraneuronal processes. The malfunction alpha-synuclein is one key events pathogenesis Parkinson disease certain other neurodegenerative diseases, there growing body evidence that two synucleins might be pathological processes system. modulation presynaptic mechanisms neurotransmission an important function synucleins, therefore, it feasible their deficiency affect global...
Aggregated forms of α-synuclein are core components pathohistological inclusions known as Lewy bodies in substantia nigra (SN) neurons patients with Parkinson's disease (PD). The role selective loss SN dopaminergic (DNs) PD is studied mice knocked out the gene. new mouse strain delta flox KO a constitutive knockout gene models end point vivo deletion conditional and has no foreign sequence modified genomic locus, thus differing from all other strains. effect neurotoxin...
Cell culturing methods in its classical 2D approach have limitations associated with altered cell morphology, gene expression patterns, migration, cycle and proliferation. Moreover, high throughput drug screening is mainly performed on cultures which are physiologically far from proper functions resulting inadequate hit-compounds subsequently fail. A shift to 3D protocols could solve issues biochemistry signaling would lead a recapitulation of physiological conditions test systems. Here, we...