A5026470826- Genetic Syndromes and Imprinting
- Neuroscience and Neuropharmacology Research
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Prenatal Screening and Diagnostics
- Tryptophan and brain disorders
- CRISPR and Genetic Engineering
- Parkinson's Disease Mechanisms and Treatments
- Biochemical effects in animals
- Medicinal Plants and Neuroprotection
- Neurological Disorders and Treatments
- Virus-based gene therapy research
- Diet and metabolism studies
- Neurological diseases and metabolism
- Plant biochemistry and biosynthesis
- Advances in Oncology and Radiotherapy
- Genetic Neurodegenerative Diseases
- Click Chemistry and Applications
- Mitochondrial Function and Pathology
- Phosphodiesterase function and regulation
- Adolescent and Pediatric Healthcare
- Neurogenetic and Muscular Disorders Research
- Genetics and Neurodevelopmental Disorders
- Acute Lymphoblastic Leukemia research
Max Delbrück Center
2024
University of California, Davis
2017-2024
MIND Research Institute
2019
University of Latvia
2010-2018
Unidad de Cirugía Artroscópica
2018
Foundation for Ichthyosis and Related Skin Types
2018
Latvia University of Life Sciences and Technologies
2018
University of Alabama at Birmingham
2016
Abstract Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by developmental delay, impaired communication, motor deficits and ataxia, intellectual disabilities, microcephaly, seizures. The genetic cause of AS the loss expression UBE3A (ubiquitin protein ligase E6-AP) in brain, typically due to deletion maternal 15q11-q13 region. Previous studies have been performed using mouse model with single exon Ube3a . Since three splice variants exist, this has led lack...
Angelman syndrome (AS) is a neurogenetic disorder caused by the loss of ubiquitin ligase E3A (UBE3A) gene expression in brain. The UBE3A paternally imprinted brain neurons. Clinical features AS are primarily due to maternally expressed A healthy copy paternal present but silenced long non-coding antisense transcript (UBE3A-ATS). Here, we demonstrate that an artificial transcription factor (ATF-S1K) can silence Ube3a-ATS adult mouse model and restore endogenous physiological Ube3a. single...
Abstract Human cell line models, including the neuronal precursor LUHMES, are important for investigating developmental transcriptional dynamics within imprinted regions, particularly 15q11-q13 Angelman (AS) and Prader-Willi (PWS) syndrome locus. AS results from loss of maternal UBE3A in neurons, where paternal allele is silenced by a convergent antisense transcript UBE3A-ATS, lncRNA that terminates at PWAR1 non-neurons. qRT-PCR analysis confirmed exclusive progressive increase UBE3A-ATS...
Abstract Polyprenols (PPs) have been identified in almost all living organisms. The richest source of PPs is the needles conifer trees. Endogenously, PPs, similarly to cholesterol, are synthesised human and animal cells via mevalonate pathway. Previous studies demonstrated anti-oxidant properties PPs. To our knowledge, no published on influence muscle strength. We hypothesised that administration could prevent changes functioning caused by statins (weakness, etc.). In present study,...
Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium) propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism is altered by inhibitors of complex I has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, investigated rat model Parkinson’s disease (PD) was generated via unilateral intrastriatal injection neurotoxin 6-hydroxydopamine (6‑OHDA). We assessed expression cell...
This review for the first time summarizes data obtained in neuropharmacological studies of mildronate, a drug previously known as cardioprotective agent. In different animal models neurotoxicity and neurodegenerative diseases, we demonstrated its neuroprotecting activity. By use immunohistochemical methods Western blot analysis, well some selected behavioral tests, new mechanisms mildronate have been demonstrated: regulatory effect on mitochondrial processes expression nerve cell proteins,...
Background. Mildronate (3-[2,2,2-trimethylhydrazinium] propionate dihydrate) traditionally is a well-known cardioprotective drug. However, our recent studies convincingly demonstrated its neuroprotective properties. The aim of the present study was to evaluate influence mildronate on expression proteins that are involved in differentiation and survival nigrostriatal dopaminergic neurons rat model Parkinson’s disease (PD). following biomarkers were used: heat shock protein 70 (Hsp70,...
Mildronate, a carnitine congener drug, previously has been shown to provide neuroprotection in an azidothymidine‐induced mouse model of neurotoxicity and Parkinson's disease rat model. The aim this study was investigate the effects mildronate treatment on cognition pathology Alzheimer's (AD) mice (APP SweDI ). Mildronate administered i.p. daily at 50 or 100 mg/kg for 28 days. At end treatment, animals were behaviorally cognitively tested, brains assessed AD‐related pathology, inflammation,...
A large subset of patients with Angelman syndrome (AS) suffer from concurrent gastrointestinal (GI) issues, including constipation, poor feeding, and reflux. AS is caused by the loss ubiquitin ligase E3A (UBE3A) gene expression in brain. Clinical features AS, which include developmental delays, intellectual disability, microcephaly, seizures, are primarily due to deficient or function maternally inherited UBE3A allele. The association between neurodevelopmental delay GI disorders part...
Ubiquitin E3 ligase 3A (UBE3A) encodes an ubiquitin whose loss from the maternal allele causes neurodevelopmental disorder Angelman syndrome (AS). Previous studies of UBE3A function have not examined full Ube3a deletion in mouse, complexity imprinted gene networks brain nor molecular basis systems-level cognitive dysfunctions AS. We therefore utilized a systems biology approach to elucidate how impacts early postnatal novel CRISPR/Cas9-engineered rat model complete deletion. Strand-specific...
Ca2+ blockers, particularly those capable of crossing the blood-brain barrier (BBB), have been suggested as a possible treatment or disease modifying agents for neurodegenerative disorders, e.g., Alzheimer's disease. The present study investigated effects novel 4-(N-dodecyl) pyridinium group-containing 1,4-dihydropyridine derivative (AP-12) on cognition and synaptic protein expression in brain. Treatment AP-12 was wild type C57BL/6J mice transgenic model (Tg APPSweDI) using behavioral tests...
SpringerPlus 2015, 4(Suppl 1):L1 MicroRNAs (miRNAs) are short, 22-25 nucleotide long transcripts that may suppress entire signaling pathways by interacting with the 3'-untranslated region (3'-UTR) of coding mRNA targets, interrupting translation and inducing degradation these targets.The 3'-UTRs brain compared to other tissues predict important roles for miRNAs.Supporting this notion, we found miRNAs co-evolved their target transcripts, non-coding pseudogenes miRNA recognition elements...
Angelman syndrome (AS) is a rare neuro-genetic disorder caused by loss of expression the maternal copy UBE3A in brain inducing severe mental and physical impairments. Due to brain-specific genetic imprinting, paternal silenced long antisense transcript. Inhibition transcript could lead unsilencing UBE3A, thus providing therapeutic approach for AS. Treatment requires widespread delivery gene regulators brain. Safe blood-brain barrier (BBB) disruption using focused ultrasound (FUS) combined...
Zinc finger (ZF), transcription activator-like effectors (TALE), and CRISPR/Cas9 therapies to regulate gene expression are becoming viable strategies treat genetic disorders, although effective in vivo delivery systems for these proteins remain a major translational hurdle. We describe the use of mesenchymal stem/stromal cell (MSC)-based system secretion ZF protein (ZF-MSC) transgenic mouse models young rhesus monkeys. Secreted from ZF-MSC was detectable within hippocampus 1 week following...
Human cell line models, including the neuronal precursor LUHMES, are important for investigating developmental transcriptional dynamics within imprinted regions, particularly 15q11-q13 Angelman (AS) and Prader-Willi (PWS) syndrome locus. AS results from loss of maternal UBE3A in neurons, where paternal allele is silenced by a convergent antisense transcript UBE3A-ATS, lncRNA that normally terminates at PWAR1 non-neurons. qRTPCR analysis confirmed exclusive progressive increase UBE3A-ATS...
The effect of harvested lymph nodes on the pN stage
Introduction: Thiopurine drugs, what are widely used medications for the treatment of inflammatory bowel diseases (IBD), have remarcable adverse effects like myelosuppression, leading to life threatening complications (severe infection or bleeding). methyltransferase (TPMT) plays a significant role in metabolism thiopurine drugs. Low TPMT activity body is associated with pathological drug metabolisms, overproduction cytotoxic metabolites and myelosuppression. Methods: A purpose our study was...