A5072348026- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
- Nuclear Receptors and Signaling
- Mitochondrial Function and Pathology
- Cell Image Analysis Techniques
- Lysosomal Storage Disorders Research
- Diet and metabolism studies
- 3D Printing in Biomedical Research
- Epigenetics and DNA Methylation
- Genetic Neurodegenerative Diseases
- Metabolism, Diabetes, and Cancer
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Metalloenzymes and iron-sulfur proteins
- Parkinson's Disease and Spinal Disorders
- Cellular transport and secretion
- Restless Legs Syndrome Research
- Plant responses to water stress
- Neurological diseases and metabolism
- Transcranial Magnetic Stimulation Studies
- Genetic Associations and Epidemiology
- RNA and protein synthesis mechanisms
- Genomics and Rare Diseases
University of Luxembourg
2014-2025
Luxembourg Institute of Health
2020-2025
Centre Hospitalier de Luxembourg
2014-2025
Hertie Institute for Clinical Brain Research
2005-2016
German Center for Neurodegenerative Diseases
2014-2016
University of Tübingen
2005-2014
University of Michigan
2012
UiT The Arctic University of Norway
2012
Washtenaw Community College
2012
Abstract Loss-of-function mutations in PARK7 , encoding for DJ-1, can lead to early onset Parkinson’s disease (PD). In mice, Park7 deletion leads dopaminergic deficits during aging, and increased sensitivity oxidative stress. However, the severity of reported phenotypes varies. To understand molecular changes upon loss we performed transcriptomic profiling midbrain sections from young mice. While at 3 months transcriptomes both male female mice were unchanged compared their wildtype...
Lewy bodies, a pathological hallmark of Parkinson's disease (PD), contain aggregated alpha-synuclein (αSyn), which is found in several modified forms and can be discovered phosphorylated, ubiquitinated truncated. Aggregation-prone truncated species αSyn caused by aberrant cleavage this fibrillogenic protein are hypothesized to participate its sequestration into inclusions subsequently leading synaptic dysfunction neuronal death. Here, we investigated the role calpain vivo generating two...
<h3>Objective</h3> To investigate predictors for improvement of disease-specific quality life (QOL) after deep brain stimulation (DBS) the subthalamic nucleus (STN) Parkinson disease (PD) with early motor complications. <h3>Methods</h3> We performed a secondary analysis data from previously published EARLYSTIM study, prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment 127) 2 years follow-up QOL (39-item Parkinson9s Disease Questionnaire summary index...
Abstract The complex and heterogeneous nature of Parkinson’s disease (PD) is still not fully understood, however, increasing evidence supports mitochondrial impairment as a major driver neurodegeneration. Miro1, GTPase encoded by the RHOT1 gene, involved in transport, mitophagy calcium buffering, therefore essential for maintaining homeostasis. Recently, Miro1 has been linked genetically pathophysiologically to PD, further supported identification heterozygous variants patients. Herein, we...
Growing evidence indicates that type 2 diabetes (T2D) is associated with an increased risk of developing Parkinson's disease (PD) through shared mechanisms. Studies show insulin resistance, which the driving pathophysiological mechanism T2D plays a major role in neurodegeneration by impairing neuronal functionality, metabolism and survival. To investigate resistance caused pathological changes human midbrain, could predispose healthy midbrain to PD development, we exposed iPSC-derived...
The protein alpha-synuclein (αSyn) plays a pivotal role in the pathogenesis of synucleinopathies, including Parkinson's disease and multiple system atrophy, with growing evidence indicating that lipid dyshomeostasis is key phenotype these neurodegenerative disorders. Previously, we identified αSyn localizes, at least part, to mitochondria-associated endoplasmic reticulum membranes (MAMs), which are transient functional domains containing proteins regulate metabolism, de novo synthesis...
Brain organoids are highly complex multi-cellular tissue proxies, which have recently risen as novel tools to study neurodegenerative diseases such Parkinson's disease (PD). However, with increasing complexity of the system, usage quantitative becomes challenging.The primary objective this was develop a neurotoxin-induced PD organoid model and assess neurotoxic effect on dopaminergic neurons using microscopy-based phenotyping in high-content fashion.We describe pipeline for machine...
Abstract Data on the frequency of α‐ synuclein mutations in Parkinson's disease (PD) are limited. Screening entire coding region 1,921 PD patients with denaturing high performance liquid chromatography and subsequent sequencing we only detected silent (g.2654A>G, g.10151G>A, g.15986A>T) c.209G>A substitution corresponding to p.A53T mutation. These results demonstrate that gene rare suggest other factors contribute aggregation majority patients. © 2005 Movement Disorder Society
While genetic causes are identified in up to 15% of all Parkinson's disease (PD) patients, the remaining idiopathic PD (iPD) patients attributed polygenic risk, environmental and lifestyle factors, interactions thereof. We applied five advanced score (PGS) tools data from 1,762 iPD 4,227 healthy controls European ancestry, resulting development a novel iPD-PGS with significantly improved discriminative performance compared existing models an AUC 0.680 (95% confidence interval (-CI): [0.665,...
Abstract MIRO1 is a mitochondrial outer membrane protein important for distribution, dynamics and bioenergetics. Over the last decade, evidence has pointed to link between Parkinson’s disease (PD) pathogenesis. Moreover, heterozygous mutation (p.R272Q) was identified in PD patient, from which an iPSC-derived midbrain organoid model derived, showing mutant-dependent selective loss of dopaminergic neurons. Herein, we use patient-specific organoids carrying p.R272Q further explore cellular...
Objectives We described waning in anti-SARS-CoV-2 IgG adult general populations infected during the first wave of COVID-19 pandemic 2020 across three European countries. Methods Coordinated analyses were conducted separately population-based cohorts with complementary follow-up schedules: KoCo19 (Germany), EpiCov (France), and CON-VINCE (Luxembourg) cohorts. Serological was based on ELISA-S (Euroimmun) assay. selected all adults aged 18–79 who had a positive serology (IgG optical density...
Abstract Background Motor fluctuations are a common complication in later stages of Parkinson's disease (PD) and significantly affect patients' quality life. Robustly identifying risk protective factors for this across distinct cohorts could lead to improved management. Objectives The goal was identify key prognostic motor PD by using machine learning exploring their associations the context prior literature. Methods We applied interpretable techniques time‐to‐event analysis prediction...
Background Despite its relevance, the clinical progression of motor- and non-motor symptoms associated with Parkinson's disease (PD) is poorly described understood, particularly in relation to sex-specific differences progression. Objective Identification differential aspects men women PD. Methods Linear mixed-model analyses 802 people typical PD from Luxembourg study's prospective cohort (median time follow-up = three years). We estimated effect moderation by sex (alpha ≤ 0.05), including...
The severity, progression, and outcomes of motor non-motor symptoms in Parkinson's disease (PD) are quite variable. Following PD cohorts holds promise for identifying predictors severity progression.
Abstract Autophagic processes play a central role in cellular homeostasis. In pathological conditions, the flow of autophagy can be affected at multiple and distinct steps pathway. Current analyses tools do not deliver required detail for dissecting pathway intermediates. The development new to analyze autophagic qualitatively quantitatively more straightforward manner is required. Defining all intermediates high-throughput technologically challenging has been addressed yet. Here, we...
Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in substantia nigra midbrain. Familial cases PD are often caused mutations PTEN-induced kinase 1 (PINK1) and ubiquitin ligase Parkin, both pivotal maintaining mitochondrial quality control. CISD1, a homodimeric iron-sulfur-binding protein, major target Parkin-mediated ubiquitination. We here discovered heightened propensity CISD1 to form dimers Pink1 mutant flies from PINK1 mutation patients. The dimer...
Abstract Mutations in THAP1 (THAP domain-containing apoptosis-associated protein 1) are responsible for DYT6 dystonia. Until now, more than eighty different mutations gene have been found patients with primary dystonia, and two third of them missense mutations. The potential pathogeneses these human largely elusive. In the present study, we generated stable transfected neuronal cell lines expressing wild-type or mutated proteins patients. Transcriptional profiling using microarrays revealed...
Preferences for risk disclosure in population-based studies assessing Parkinson's disease (PD) have not been assessed so far. To examine preferences a subset of the European Healthy Brain Aging (HeBA) multicenter study. After remote PD assessment, structured pilot-questionnaire on was first presented to participants (≥50 years, without neurodegenerative diseases) during in-person visits at Innsbruck study site. From included 81 (63% females, median age 65 years), 79% expressed an...
Abstract A major challenge in the field of neurodegenerative diseases is poor translation pre-clinical models to clinical applications. The human brain an immensely complex structure, which makes it difficult recapitulate its development, function and disorders. In recent years, organoids derived from induced pluripotent stem cells have risen as novel tools study such Parkinson’s disease (PD). PD a multifactorial disorder, with aging, genetics environmental factors key etiological elements....
Background: To establish the frequency of impulse control disorder (ICD) in Parkinson's disease (PD). Methods: Within Luxembourg Study, PD patients were evaluated for ICD presence (score ≥ 1 on MDS-UPDRS I item 1.6), use dopamine agonists (DA) and other medications. Results: 470 enrolled. Among 217 without DA use, 6.9% scored positive ICD, vs. 15.4% among 253 with ( p = 0.005). The regression analysis showed that age at diagnosis had only a minor impact occurrence, while there was no...
BACKGROUNDHeterozygous variants in the gene glucocerebrosidase (GBA1) causing Gaucher’s disease, a recessive lysosomal storage disorder, are involved Parkinson’s disease (PD) pathogenesis. An association of those Gaucher-related GBA1 with progression non-motor symptoms PD has been reported but role Parkinson’s-risk (PD-risk) is less clear. Analysis longitudinal changes motor- and carriers different compared to non-carriers could elucidate their pathogenic relevance.OBJECTIVESTo compare...