A5004744908- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Muscle Physiology and Disorders
- Parathyroid Disorders and Treatments
- Lipoproteins and Cardiovascular Health
- Biomedical Research and Pathophysiology
- Bone health and treatments
- Hemoglobinopathies and Related Disorders
- Liver Disease Diagnosis and Treatment
- Neurological disorders and treatments
- Erythrocyte Function and Pathophysiology
- Diabetes and associated disorders
- Folate and B Vitamins Research
- Neurological diseases and metabolism
- Hereditary Neurological Disorders
- Dermatological and Skeletal Disorders
- Cancer, Lipids, and Metabolism
- Liver Disease and Transplantation
- Thyroid Disorders and Treatments
- Immunodeficiency and Autoimmune Disorders
- Neonatal Health and Biochemistry
- Cancer, Hypoxia, and Metabolism
- Lipid metabolism and disorders
- Ubiquitin and proteasome pathways
Universität Ulm
2010-2024
University Hospital Ulm
2012-2021
Heidelberg University of Education
2017
Harvard University
2004-2010
Massachusetts General Hospital
2004-2010
University of Auckland
2010
University Medical Center Freiburg
2010
École Polytechnique Fédérale de Lausanne
2010
MaineGeneral Medical Center
2006-2010
Medical University of the Americas
2006
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...
Abstract Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the IT‐15 gene; however, it remains unknown how mutation leads to selective neurodegeneration. Several lines of evidence suggest impaired mitochondrial function as component process HD. We assessed energy metabolism skeletal muscle 15 HD patients and 12 asymptomatic carriers vivo using 31P magnetic resonance spectroscopy. Phosphocreatine recovery after...
Objective: Most cardiac myosin binding protein C (cMyBP-C) gene mutations causing familial hypertrophic cardiomyopathy (FHC) result in C-terminal truncated proteins. However, cMyBP-Cs were undetectable myocardial tissue of FHC patients. In the present study, we investigated whether are subject to accelerated degradation by lysosome or ubiquitin–proteasome system (UPS).
Intracellular aggregates commonly forming neuronal intranuclear inclusions are neuropathological hallmarks of spinocerebellar ataxia type 3 and other disorders characterized by expanded polyglutamine-(poly-Q) tracts. To characterize cellular responses to these aggregates, we performed an immunohistochemical analysis in pontine neurons patients affected 3, using a panel antibodies directed against chaperones proteasome subunits. A subset the stained positively for Hsp90alpha HDJ-2, member...
A semi professional marathon runner at risk for Huntington's disease (HD) (43 CAG repeats) developed signs of a slowly progressive myopathy with exercise-induced muscle fatigue, pain, elevated creatine kinase level, and worsening his running performance many years before first chorea were detected. Muscle biopsy displayed mild mitochondrial pathology including complex IV deficiency analysis the patient's fibroblast culture demonstrated deficits in function. Challenging skeletal by excessive...
Abstract Objective The aim of the present work was detection Mitochondrial dysfunction Huntington's disease (HD). Methods We investigated muscle and mitochondria 14‐ to 16‐week‐old R6/2 mice in comparison with wild‐type mice. Results Atrophic fibers, increased fuchsinophilic aggregates, reduced cytochrome c oxidase (15%) were found HD muscle. With swelling measurements Ca 2+ accumulation experiments, a decreased stability against ‐induced permeability transition detected. Complex I–dependent...
Aberrant mitochondrial function, morphology, and transport are main features of neurodegenerative diseases. To date, within neurons is thought to rely mainly on microtubules, whereas actin might mediate short-range movements anchoring. Here, we analyzed the impact neuronal size localization. F-actin enhanced number in neurites growth cones. In contrast, raising G-actin resulted fragmentation decreased abundance. Cellular F-actin/G-actin levels also regulate serum response factor...
Neurodegenerative diseases are characterized by distinct patterns of neuronal loss. In amyotrophic lateral sclerosis (ALS) upper and lower motoneurons degenerate whereas in Huntington's disease (HD) medium spiny neurons the striatum preferentially affected. Despite these differences pathophysiological mechanisms risk factors remarkably similar. addition, non-neuronal features, such as weight loss implicate a dysregulation energy metabolism. Mammalian sirtuins, especially mitochondrial NAD+...
Motor speech alterations are a prominent feature of clinically manifest Huntington's disease (HD). Objective acoustic analysis can quantify alterations. It is currently unknown, however, at what stage HD be reliably detected. We aimed to explore the patterns and extent using objective in assess correlations with both rater-assessed phenotypical features biological determinants HD.Speech samples were acquired from 44 premanifest (29 pre-symptomatic 15 prodromal) 25 gene expansion carriers,...
Spinocerebellar ataxia 7 (SCA7) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG‐trinucleotide repeat in coding region SCA7 gene. The translated into extended polyglutamine stretch protein ataxin‐7, unknown function. By Northern blot analysis expression ataxin‐7 was detected numerous regions human brain and some peripheral tissues. It unknown, however, if enriched at sites pathology. We studied regional cellular pattern mRNA level situ hybridization...
Abstract Polyglutamine (polyQ) expansion in many proteins, including huntingtin and ataxin‐3, is pathogenic responsible for neuronal dysfunction degeneration. Although at least nine neurodegenerative diseases are caused by expanded polyQ, the pathogenesis of these still not well understood. In present study, we used Caenorhabditis elegans to study molecular mechanism polyQ‐mediated toxicity. We expressed full‐length truncated ataxin‐3 with different lengths polyQ nervous system C. . show...
Huntington’s disease (HD) is caused by an expanded CAG trinucleotide repeat within the gene encoding protein huntingtin. The resulting elongated glutamine (poly-Q) sequence of mutant huntingtin (mhtt) affects both central neurons and skeletal muscle. Recent reports suggest that ryanodine receptor–based Ca2+ signaling, which crucial for muscle excitation–contraction coupling (ECC), changed mhtt in HD neurons. Consequently, we searched alterations ECC fibers R6/2 mouse, a mouse model HD. We...
Motor dysfunction, cognitive impairment, and regional cortical atrophy indicate cerebral involvement in Huntington disease (HD). To address the hypothesis that abnormal corticostriatal connectivity arises from polyglutamine-related alterations gene expression, we isolated layer 5 neurons by laser-capture microdissection analyzed transcriptome-wide mRNA changes them. Enrichment of transcription factor mRNAs including foxp2, tbr1, neuroD6, neurotransmission- plasticity-related RNAs sema5A,...
Huntington´s disease (HD) is a hereditary neurodegenerative resulting from an expanded polyglutamine sequence (poly-Q) in the protein huntingtin (HTT). Various studies report atrophy and metabolic pathology of skeletal muscle HD suggest as part process fast-to-slow fiber type transition that may be caused by pathological changes central motor control or/and mutant HTT tissue itself. To investigate HD, we used R6/2 mice, common animal model for rapidly progressing variant expressing exon 1...
Abstract Background A declining cognitive performance is a hallmark of Huntington’s disease (HD). The neuropsychological battery the Unified HD Rating Scale (UHDRS'99) commonly used for assessing cognition. However, there need to identify and minimize impact confounding factors, such as language, gender, age, education level on decline. Objectives Aim provide appropriate, normative data allow clinicians disease-associated decline in diverse populations by compensating factors Methods Sample...
The recent discovery of active brown fat in human adults has led to renewed interest the role this key metabolic tissue. This is particularly true for neurodegenerative conditions like Huntington disease (HD), an adult-onset heritable disorder with a prominent energy deficit phenotype. Current methods imaging adipose tissue (BAT) are limited use because they equipment-wise demanding and often prohibitively expensive. prompted us explore how standard MRI set-up can be modified visualize BAT...
The huntingtin-associated protein 40 (HAP40) is an abundant interactor of huntingtin (HTT). In complexes these proteins, HAP40 tightly binds to HTT in a cleft formed by two larger domains rich HEAT repeats, and smaller bridge domain connecting the two. We show that steady-state levels are directly dependent on (both normal mutant HTT) strongly stabilized interaction with resulting at least 5-fold increase HAP40's half-life when bound HTT. Cellular were reduced primary fibroblasts...