A5070026591- Parkinson's Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Metabolomics and Mass Spectrometry Studies
- Cancer, Hypoxia, and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Health, Environment, Cognitive Aging
- Genomics, phytochemicals, and oxidative stress
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Immune cells in cancer
- Autophagy in Disease and Therapy
- Neurological diseases and metabolism
- ATP Synthase and ATPases Research
- Retinoids in leukemia and cellular processes
- Neurological and metabolic disorders
- Indoor Air Quality and Microbial Exposure
- Lipid metabolism and biosynthesis
- Diet and metabolism studies
- Tryptophan and brain disorders
- Phytochemistry and Bioactive Compounds
- Cell Image Analysis Techniques
- Phytochemical Studies and Bioactivities
- Genetics and Neurodevelopmental Disorders
- Synthesis and biological activity
- Hedgehog Signaling Pathway Studies
University of Luxembourg
2013-2024
Hôpital Kirchberg
2010-2014
Immunoresponsive gene 1 ( Irg1 ) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. Here, we identify as the coding for an enzyme producing itaconic acid (also known methylenesuccinic acid) through decarboxylation of cis -aconitate, a tricarboxylic cycle intermediate. Using gain-and-loss-of-function approach both mouse and human immune cells, found expression levels correlating with amounts acid, metabolite previously...
Idiopathic Parkinson's disease is characterized by a progressive loss of dopaminergic neurons, but the exact aetiology remains largely unknown. To date, research has mainly focused on nigral although recent studies suggest disease-related changes also in non-neuronal cells and midbrain regions beyond substantia nigra. While there some evidence for glial involvement disease, molecular mechanisms remain poorly understood. The aim this study was to characterize contribution all cell types...
There is increasing evidence for a role of inflammation in Parkinson's disease. Recent research murine models suggests that parkin and PINK1 deficiency leads to impaired mitophagy, which causes the release mitochondrial DNA (mtDNA), thereby triggering inflammation. Specifically, CGAS (cyclic GMP-AMP synthase)-STING (stimulator interferon genes) pathway mitigates activation innate immune system, quantifiable as increased interleukin-6 (IL6) levels. However, IL6 circulating cell-free mtDNA...
Proper sample preparation is an integral part of all omics approaches, and can drastically impact the results a wide number analyses. As metabolomics proteomics research approaches often yield complementary information, it desirable to have procedure which information for both types analyses from same cell population. This protocol explains method separation isolation metabolites proteins biological sample, in order downstream use simultaneously. In this way, two different levels regulation...
Mutations in the E3 ubiquitin ligase parkin cause autosomal recessive Parkinson's disease (PD). Together with PTEN-induced kinase 1 (PINK1), regulates clearance of dysfunctional mitochondria. New mitochondria are generated through an interplay nuclear- and mitochondrial-encoded proteins, recent studies suggest that influences this process at both levels. In addition, was shown to prevent mitochondrial membrane permeability, impeding DNA (mtDNA) escape subsequent neuroinflammation. However,...
Aims: The outer mitochondrial membrane protein Miro1 is a crucial player in dynamics and calcium homeostasis. Recent evidence indicated that mediates calcium-induced shape transition, which prerequisite for the initiation of mitophagy. Moreover, altered levels have emerged as shared feature monogenic sporadic Parkinson's disease (PD), but, so far, no disease-associated variants RHOT1 been identified. Here, we aim to explore genetic functional contribution mutations PD patient-derived...
The oncogene DJ-1 has been originally identified as a suppressor of PTEN. Further on, loss-of-function mutations have described causative factor in Parkinson's disease (PD). an important function cellular antioxidant responses, but its role central metabolism neurons is still elusive. We applied stable isotope assisted metabolic profiling to investigate the effect functional loss and show that deficient neuronal cells exhibit decreased glutamine influx reduced serine biosynthesis. By...
Parkinson's Disease is the second most common neurodegenerative disorder worldwide, with growing numbers and considerable societal economic concerns. Human cell culture systems are efficient models for disorders allow personalized, non-invasive analysis of cellular molecular disease mechanisms. Midbrain organoids assembloids advanced 3D that recapitulate human midbrain, which highly affected by disease. Here, we used healthy control patient-specific midbrain to assess mitochondrial DNA...
Increased proliferation rates as well resistance to apoptosis are considered major obstacles for the treatment of patients with chronic myelogenous leukemia (CML), thus highlighting need novel therapeutic approaches.Since senescence has been recognized a physiological barrier against tumorigenesis, senescence-based therapy could represent new strategy CML.DNA demethylating agent 5-aza-2′-deoxycytidine (DAC) was reported induce cellular but underlying mechanisms remain be elucidated.Here, we...
Several mutations in Leucine-rich repeat kinase-2 (LRRK2) have been associated with Parkinson's disease (PD). The most common substitution, G2019S, interferes LRRK2 kinase activity, which is regulated by autophosphorylation. Yet, the penetrance of this gain-of-function mutation incomplete, and thus far, few factors correlated status carriers. This includes (i) autophosphorylation urinary exosomes, (ii) serum levels antioxidant urate, (iii) abundance mtDNA transcription-associated 7S DNA. In...
Abstract Biallelic mutations in PINK1/PRKN cause recessive Parkinson’s disease. Given the established role of PINK1/Parkin regulating mitochondrial dynamics, we explored DNA integrity and inflammation as disease modifiers carriers these genes. Mitochondrial was investigated a large collection biallelic (n = 84) monoallelic 170) mutations, idiopathic patients 67) controls 90). In addition, studied global gene expression serum cytokine levels subset. Affected unaffected mutation can be...
Abstract ACO2 is a mitochondrial protein, which critically involved in the function of tricarboxylic acid cycle (TCA), maintenance iron homeostasis, oxidative stress defense and integrity DNA (mtDNA). Mutations gene were identified patients suffering from broad range symptoms, including optic nerve atrophy, cortical cerebellar hypotonia, seizures intellectual disabilities. In present study, we heterozygous 51 bp deletion (c.1699_1749del51) family with autosomal dominant inherited isolated...
Abstract Background Astrocytes have recently gained attention as key contributors to the pathogenesis of neurodegenerative disorders including Parkinson’s disease. To investigate human astrocytes in vitro, numerous differentiation protocols been developed. However, properties resulting glia are inconsistent, which complicates selection an appropriate method for a given research question. Thus, we compared two approaches generation iPSC-derived astrocytes. We phenotyped that were obtained...
Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are a primary monogenic cause of Parkinson’s disease (PD). However, likelihood developing PD with inherited LRRK2 pathogenic differs (a phenomenon known as “reduced penetrance”), factors including age and geographic region, highlighting potential role for lifestyle environmental onset. To investigate this, household dust samples from four different groups individuals were analyzed using metabolomics/exposomics metagenomics...
Using an untargeted stable isotope-assisted metabolomics approach, we identify erythronate as a metabolite that accumulates in several human cancer cell lines. Erythronate has been reported to be detoxification product derived from off-target glycolytic metabolism. We use chemical inhibitors and genetic silencing define the pentose phosphate pathway intermediate erythrose 4-phosphate (E4P) starting substrate for production. However, following enzyme assay-coupled protein fractionation...
Abstract Using a non-targeted isotope-assisted metabolomics approach, we identified erythronate as metabolite that accumulates in several human cancer cell lines. Erythronate has been reported to be detoxification product derived from off-target glycolytic metabolism. We provide data supporting possible alternative route production involving the dephosphorylation of pentose phosphate pathway intermediate erythrose-4-phosphate form erythrose, followed by oxidation erythrose an aldehyde...