A5051768163- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Neuroscience and Neuropharmacology Research
- Muscle Physiology and Disorders
- Ubiquitin and proteasome pathways
- Parkinson's Disease Mechanisms and Treatments
- RNA Research and Splicing
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Autophagy in Disease and Therapy
- Neurotransmitter Receptor Influence on Behavior
- Hereditary Neurological Disorders
- Cancer Genomics and Diagnostics
- Hepatocellular Carcinoma Treatment and Prognosis
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Genomic variations and chromosomal abnormalities
- Adipose Tissue and Metabolism
- Calpain Protease Function and Regulation
- Nerve injury and regeneration
- Acute Myeloid Leukemia Research
- Genetic factors in colorectal cancer
- Neurogenesis and neuroplasticity mechanisms
- Genomics and Chromatin Dynamics
- MicroRNA in disease regulation
Ruhr University Bochum
2018-2025
Ho Chi Minh City Medicine and Pharmacy University
2018-2025
Katholisches Klinikum Bochum
2025
Korea Advanced Institute of Science and Technology
2024
Nong Lam University Ho Chi Minh City
2024
Historical Association
2024
Yerevan State Medical University
2019-2024
University Medical Center HCMC
2022
Tay Bac University
2022
University of Tübingen
2012-2021
Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of CAG trinucleotide repeat more than 39 units gene unknown function. Several mouse models have been reported which show rapid progression phenotype leading to death within 3–5 months (transgenic models) resembling the rare juvenile course HD (Westphal variant) or do not present with any symptoms (knock-in mice). Owing small size brain, mice are suitable for repetitive vivo imaging...
α-Synuclein (α-syn) has been implicated in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease. These disorders are characterized by various neurological and psychiatric symptoms based on progressive neuropathological alterations. Whether process might be halted or even reversed is presently unknown. Therefore, conditional mouse models powerful tools to analyze relationship between transgene expression progression To explore whether α-syn solely originates...
Brain cholesterol, which is synthesized locally, a major component of myelin and cell membranes participates in neuronal functions, such as membrane trafficking, signal transduction, neurotransmitter release, synaptogenesis. Here we show that brain cholesterol biosynthesis reduced multiple transgenic knock-in Huntington's disease (HD) rodent models, arguably dependent on deficits mutant astrocytes. Mice carrying progressively increased number CAG repeats more evident reduction biosynthesis....
Huntington disease (HD) is caused by a polyglutamine expansion of more than 35 units in the huntingtin protein. This expanded repeat length inversely correlates with age-at-onset (AAO), however, additional genetic factors apart from CAG size are thought to influence course and AAO HD. Until now, among others, gene encoding PCG-1α (PPARGC1A) was shown modify two independent, however small, populations. PGC-1α involved induction various mechanisms regulating mitochondrial biogenesis oxidative...
The expanded HTT CAG repeat causing Huntington's disease (HD) exhibits somatic expansion proposed to drive the rate of onset by eliciting a pathological process that ultimately claims vulnerable cells. To gain insight into in humans, we performed comprehensive quantitative analyses ~50 central nervous system (CNS) and peripheral postmortem tissues from seven adult-onset one juvenile-onset HD individual. We also assessed ATXN1 brain regions an individual with neurologically pathologically...
Cytogenetic diagnostics play a crucial role in risk stratification and classification of myeloid malignancies such as acute leukemia (AML) myelodysplastic syndrome (MDS), thus influencing treatment decisions. Optical genome mapping (OGM) is novel whole method for the detection cytogenetic abnormalities. Our study assessed applicability practicality OGM diagnostic tool AML MDS patients. In total, 27 patients with or underwent routine including classical karyotyping fluorescence situ...
Abstract Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, 3-year prospective study, we evaluated novel diagnostic concept based on multidisciplinary expertise in Germany. Here present the systematic investigation of phenotypic and molecular genetic data 1,577 patients who had undergone exome sequencing were partially analyzed next-generation phenotyping approaches....
Although NH2-terminal mutant huntingtin (htt) fragments cause neurological disorders in Huntington's disease (HD), it is unclear how toxic htt are generated and contribute to the process. Here, we report that complex smaller than first 508 amino acids were htt-transfected cells HD knockin mouse brains. These constituted neuronal nuclear inclusions appeared before symptoms. The accumulation aggregation of these associated with an age-dependent decrease proteasome activity promoted by...
Huntington's disease (HD) is caused by a polyglutamine expansion in the protein huntingtin. The causes huntingtin to interact abnormally with number of proteins. However, it unclear whether, and how, huntingtin-associated proteins are involved neurodegeneration HD. Here, we show that protein-1 (HAP1), which intracellular trafficking epidermal growth factor receptor (EGFR), highly expressed hypothalamus. Mice lacking HAP1 die after birth because depressed feeding activity. Terminal...
Recent clinical studies have highlighted that female sex hormones represent potential neuroprotective mediators against damage caused by acute and chronic brain diseases. This evidence has been confirmed experimental documenting the protective role of both in vitro vivo, although these did not specifically focus on Huntington's disease (HD). We therefore investigated onset course HD male transgenic (tg) (CAGn51) control rats across age focused three aspects: (i) behavioral physiological...
Cellular proliferation, differentiation, integration, and survival within the adult neural stem cell niche are altered under pathological conditions, but molecular cues regulating biology of this mostly unknown. We examined hippocampal in a transgenic rat model Huntington disease. In model, progressive cognitive deficits develop at age 9months, suggesting possible dysfunction. found disease-associated decline progenitor proliferation accompanied by an expansion pool 5-bromo-2-deoxyuridine...
Huntington disease (HD) is an inherited progressive neurodegenerative disorder, characterized by motor, cognitive, and psychiatric deficits as well neurodegeneration brain atrophy beginning in the striatum cortex extending to other subcortical regions. The genetic cause expansion of CAG repeat stretch HTT gene encoding huntingtin protein (htt). Here, we generated HD transgenic rat model using a human bacterial artificial chromosome (BAC), which contains full-length genomic sequence with 97...
White matter (WM) atrophy is a significant feature of Huntington disease (HD), although its aetiology and early pathological manifestations remain poorly defined. In this study, we aimed to characterize WM-related features in the transgenic YAC128 BACHD models HD. Using diffusion tensor magnetic resonance imaging (DT-MRI), demonstrate that microstructural WM abnormalities occur from an age mice. Similarly, electron microscopy analysis myelinated fibres corpus callosum indicated myelin...
We report a novel experimental immunotherapeutic approach in patient with metastatic intrahepatic cholangiocarcinoma. In the 5year course of disease, initial tumor mass, two local recurrences and lung metastasis were surgically removed. Lacking alternative treatment options, aiming at induction anti-tumor T cells responses, we initiated personalized multi-peptide vaccination, based on in-depth analysis antigens (immunopeptidome) sequencing.Tumors characterized by immunohistochemistry,...
Intrastriatal administration of mesenchymal stem cells (MSCs) has shown beneficial effects in rodent models Huntington disease (HD). However, the invasive nature surgical procedure and its potential to trigger host immune response may limit clinical use. Hence, we sought evaluate non-invasive intranasal (INA) MSC delivery as an effective alternative route HD. GFP-expressing MSCs derived from bone marrow were intranasally administered 4-week-old R6/2 HD transgenic mice. detected olfactory...
Huntington's disease (HD) is caused by an expanded CAG repeat leading to the synthesis of aberrant protein and formation polyglutamine (polyQ)-containing inclusions aggregates. Limited information available concerning association neuropathological markers with development behavioral in HD. Using a previously generated transgenic rat model HD (tgHD rat), we performed studies on time-course symptoms (motor function, learning, anxiety) appearance striatal atrophy, 1C2 immunopositive aggregates...
A polyglutamine repeat expansion of more than 36 units in a protein called huntingtin (htt) is the only known cause Huntington's disease (HD). The expanded length inversely correlated with age-at-onset (AAO), however, onset age among HD patients CAG repeats below 60 varies considerably. In addition to environmental factors, genetic factors different from can modify AAO HD. We hypothezised that htt interacting proteins might contribute this variation and investigated human htt-associated...
Huntington disease (HD) is characterized by polyglutamine expansions of huntingtin (htt), but the underlying pathomechanisms have remained unclear. We studied brain mitochondria transgenic HD rats with 51 glutamine repeats (htt51Q), modeling adult form HD. (Cafree2+) up to 2 μm activated state 3 respiration wild type glutamate/malate or pyruvate/malate as substrates. above inhibited via cyclosporin A-dependent permeability transition (PT). Ruthenium red, an inhibitor mitochondrial Ca2+...