Wolfram S. Kunz
A5089900835- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Epilepsy research and treatment
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Genomics and Rare Diseases
- Genetic Neurodegenerative Diseases
- Ion channel regulation and function
- Adipose Tissue and Metabolism
- Advanced MRI Techniques and Applications
- Diet and metabolism studies
- Pharmacological Effects and Toxicity Studies
- Cardiac Ischemia and Reperfusion
- Genomic variations and chromosomal abnormalities
- Metabolomics and Mass Spectrometry Studies
- Neurogenetic and Muscular Disorders Research
- Amyotrophic Lateral Sclerosis Research
- Skin and Cellular Biology Research
- Parkinson's Disease Mechanisms and Treatments
- Electron Spin Resonance Studies
- Glycogen Storage Diseases and Myoclonus
- RNA and protein synthesis mechanisms
- Gastrointestinal motility and disorders
- Redox biology and oxidative stress
Heidelberg University
2013-2025
German Cancer Research Center
2013-2025
University of Bonn
2015-2024
University Hospital Bonn
2011-2024
Life & Brain (Germany)
2012-2022
Boston Children's Hospital
2022
University of Tübingen
1997-2022
University of Cologne
2002-2022
Hertie Institute for Clinical Brain Research
2022
Center for Behavioral Brain Sciences
2022
Mitochondrial respiratory chain complexes I and III have been shown to produce superoxide but the exact contribution localization of individual sites remained unclear. We approached this question investigating effects oxygen, substrates, inhibitors, NAD+/NADH redox couple on H2O2 production isolated mitochondria from rat human brain. Although brain in presence glutamate+malate alone do generate only small amounts (0.04 ± 0.02 nmol H2O2/min/mg), a substantial is observed after addition...
The epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report genome-wide mega-analysis involving 15,212 individuals with epilepsy 29,677 controls, which reveals 16 significant loci, of 11 are novel. Using various prioritization criteria, we pinpoint the 21 most likely genes at these majority in genetic generalized epilepsies. These diverse biological functions, including coding for ion-channel subunits, transcription factors...
Parkinson's disease (PD) is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations the mitochondrial protein kinase PINK1 (PTEN induced putative 1) cause recessive PARK6 variant PD.Now we generated a deficient mouse and observed several novel phenotypes: A progressive reduction weight locomotor activity selectively for spontaneous movements occurred at old age. As in PD, abnormal dopamine levels aged nigrostriatal projection...
Abstract Emerging gene therapy approaches that aim to eliminate pathogenic mutations of mitochondrial DNA (mtDNA) rely on efficient degradation linearized mtDNA, but the enzymatic machinery performing this task is presently unknown. Here, we show that, in cellular models restriction endonuclease-induced mtDNA double-strand breaks, linear eliminated within hours by exonucleolytic activities. Inactivation 5′-3′exonuclease MGME1, elimination 3′-5′exonuclease activity polymerase POLG introducing...
Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was first to be genetically defined by a point mutation in DNA (mtDNA). A molecular diagnosis achieved up 95% of cases, vast majority which are accounted for 3 mutations within complex I subunit–encoding genes mtDNA (mtLHON). Here, we resolve enigma LHON absence pathogenic mutations. We describe biallelic nuclear encoded gene, DNAJC30, 33 unsolved patients from 29 families establish an autosomal...
Human mitochondrial DNA (mtDNA) is a 16.5-kb, circular genome essential for the maintenance of function and present in multiple copies most cell types. High sequence divergence maternal inheritance make mtDNA useful tracing human lineages. Whether recombination occurs
Mitochondria are cellular organelles crucial for energy supply and calcium homeostasis in neuronal cells, their dysfunction causes seizure activity some rare human epilepsies. To directly test whether mitochondrial respiratory chain enzymes abnormal the most common form of chronic epilepsy, temporal lobe epilepsy (TLE), living brain specimens from 57 epileptic patients 2 nonepileptic controls were investigated. In TLE with a hippocampal focus, we demonstrated specific deficiency complex I...
Dysfunction of plectin, a 500-kD cytolinker protein, leads to skin blistering and muscular dystrophy. Using conditional gene targeting in mice, we show that plectin deficiency results progressive degenerative alterations striated muscle, including aggregation partial loss intermediate filament (IF) networks, detachment the contractile apparatus from sarcolemma, profound changes myofiber costameric cytoarchitecture, decreased mitochondrial number function. Analysis newly generated...
Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% all epilepsies. Despite their high heritability 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out two-stage genome-wide association study (GWAS) including 3020 patients with 3954 controls European ancestry. dissect syndrome-related variants, also explored two distinct subgroups comprising 1434...
Abstract Nanobodies represent the variable binding domain of camelid heavy-chain antibodies and are employed in a rapidly growing range applications biotechnology biomedicine. Their success is based on unique properties including their reported ability to reversibly refold after heat-induced denaturation. This view, however, contrasted by studies which involve irreversibly aggregating nanobodies, asking for quantitative analysis that clearly defines nanobody thermoresistance reveals...