A5073864628- Tuberous Sclerosis Complex Research
- MicroRNA in disease regulation
- Epilepsy research and treatment
- Trace Elements in Health
- Pharmacological Effects and Toxicity Studies
- Barrier Structure and Function Studies
- Histiocytic Disorders and Treatments
- Protease and Inhibitor Mechanisms
- Renal and related cancers
- Drug Transport and Resistance Mechanisms
- Ubiquitin and proteasome pathways
- Diet and metabolism studies
- Nanoparticle-Based Drug Delivery
- Neuroinflammation and Neurodegeneration Mechanisms
- Circular RNAs in diseases
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Extracellular vesicles in disease
- Clinical Nutrition and Gastroenterology
- Angiogenesis and VEGF in Cancer
- Computational Drug Discovery Methods
- Algal biology and biofuel production
- Tumors and Oncological Cases
- Kruppel-like factors research
University of Amsterdam
2016-2025
Amsterdam University Medical Centers
2018-2025
Amsterdam Neuroscience
2018-2025
Icahn School of Medicine at Mount Sinai
2023-2024
Allen Institute for Brain Science
2023
Vrije Universiteit Amsterdam
2019
Amsterdam UMC Location University of Amsterdam
2016-2019
Summary Objective Because brain inflammation may contribute to the pathophysiology of temporal lobe epilepsy ( TLE ), we investigated expression various inflammatory markers innate and adaptive immune system in epileptogenic human rat hippocampus relation seizure activity blood‐brain barrier BBB ) dysfunction. Methods Immunohistochemistry was performed using cell (for microglia, monocytes, macrophages, T lymphocytes, dendritic cells) on hippocampal sections drug‐resistant patients who died...
Abstract Temporal lobe epilepsy (TLE) is a chronic neurological disease in humans, which refractory to pharmacological treatment about 30% of the patients. Reactive glial cells are thought play major role during development (epileptogenesis) via regulation brain inflammation and remodeling extracellular matrix (ECM). These processes can be regulated by microRNAs (miRs), class small non‐coding RNAs, control entire gene networks at post‐transcriptional level. The expression miRs known change...
Abstract Neuronal dysfunction due to iron accumulation in conjunction with reactive oxygen species (ROS) could represent an important, yet underappreciated, component of the epileptogenic process. However, date, alterations metabolism brain have not been addressed detail. Iron-related neuropathology and antioxidant metabolic processes were investigated resected tissue from patients temporal lobe epilepsy hippocampal sclerosis (TLE-HS), post-mortem who died after status epilepticus (SE) as...
Matrix metalloproteinases (MMPs) are synthesized by neurons and glia released into the extracellular space, where they act as modulators of neuroplasticity neuroinflammatory agents. Development epilepsy (epileptogenesis) is associated with increased expression MMPs, therefore, may represent potential therapeutic drug targets. Using quantitative PCR (qPCR) immunohistochemistry, we studied MMPs their endogenous inhibitors tissue (TIMPs) in patients status epilepticus (SE) or temporal lobe...
Inflammatory processes induced by brain injury are important for recovery; however, when uncontrolled, inflammation can be deleterious, likely explaining why most anti-inflammatory treatments have failed to improve neurological outcomes after in clinical trials. In the thalamus, chronic activation of glial cells, a proxy inflammation, has been suggested as an indicator increased seizure risk and cognitive deficits that develop cortical injury. Furthermore, lesions more than other regions,...
Temporal lobe epilepsy (TLE) is a chronic neurological disease, in which about 30% of patients cannot be treated adequately with anti-epileptic drugs. Brain inflammation and remodeling the extracellular matrix (ECM) seem to play major role TLE. Matrix metalloproteinases (MMPs) are proteolytic enzymes largely responsible for ECM. The inhibition MMPs has been suggested as novel therapy epilepsy; however, available MMP inhibitors lack specificity cause serious side effects. We studied whether...
Traumatic brain injury (TBI) is associated with the pathological activation of immune-competent cells in brain, such as astrocytes, microglia and infiltrating immune blood cells, resulting chronic inflammation gliosis. This may contribute to secondary after TBI, thus understanding these processes crucial for development effective treatments post-traumatic pathologies. MicroRNAs (miRNAs, miRs) are small noncoding RNAs, functioning posttranscriptional regulators gene expression. The increased...
Abstract SorCS2 is an intracellular sorting receptor of the VPS10P domain gene family recently implicated in oxidative stress response. Here, we interrogated relevance stress‐related activities brain by exploring its role ischemic stroke mouse models and patients. Although primarily seen neurons healthy brain, expression was massively induced astrocytes surrounding core mice following stroke. Post‐stroke induction likely a result increased levels transforming growth factor β1 damaged tissue,...
Abstract Aims Focal cortical dysplasia (FCD) type 2 is an epileptogenic malformation of the neocortex associated with somatic mutations in mammalian target rapamycin (mTOR) pathway. Histopathologically, FCD subdivided into 2a and 2b, only discriminator being presence balloon cells (BCs) 2b. While pro‐epileptogenic immune system activation inflammatory responses are commonly detected both subtypes, it unknown what contextual role BCs play. Methods The present study employed RNA sequencing...
Down syndrome (DS) is the most common genetic cause of intellectual disability, resulting from trisomy chromosome 21. The main feature DS neuropathology includes early onset Alzheimer's disease (AD), with deposition senile plaques and tangles. We hypothesized that apoptosis may be activated in presence AD DS, thus we measured proteins associated upstream downstream pathways p53 frontal cortex cases without pathology Ts65Dn mice, at different ages. observed increased acetylation...
Abstract Astrocytes are important mediators of inflammatory processes in the brain and seem to play an role several neurological disorders, including epilepsy. Recent studies show that astrocytes produce microRNAs, which may function as crucial regulators pathways could be used therapeutic target. We aim study miRNAs produced by during IL‐1β mediated conditions vitro, well their functional validate these findings human epileptogenic tissue. Sequencing was assess miRNA mRNA expression...
The proteasome is a multisubunit enzyme complex involved in protein degradation, which essential for many cellular processes. During inflammation, the constitutive subunits are replaced by their inducible counterparts, resulting formation of immunoproteasome. We investigated expression pattern (β1, β5) and immunoproteasome (β1i, β5i) using immunohistochemistry malformations cortical development (MCD; focal dysplasia (FCD) IIa b, tubers from patients with tuberous sclerosis (TSC), mild MCD...
Aim Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) control proteolysis within the extracellular matrix (ECM) of brain. Dysfunction this enzymatic system due to brain inflammation can disrupt blood‐brain barrier (BBB) has been implicated in pathogenesis epilepsy. However, not extensively studied epileptogenic human Methods We investigated expression cellular localization major MMPs (MMP2, MMP3, MMP9 MMP14) TIMPs (TIMP1, TIMP2, TIMP3 TIMP4) using quantitative...
Introduction Constitutive activation of the mTOR pathway, as observed in Tuberous Sclerosis Complex (TSC), leads to glial dysfunction and subsequent epileptogenesis. Although astrocytes are considered important mediators for synaptic clearance phagocytosis, little is known on how contribute epileptogenic network. Methods We employed singlenuclei RNA sequencing a hybrid fetal calf serum (FCS)/FCS-free cell culture model explore capacity TSC-derived maintain glutamate homeostasis clear debris...
Inhibition of the mammalian target rapamycin (mTOR) pathway reduces epileptogenesis in various epilepsy models, possibly by inhibition inflammatory processes, which may include proteasome system. To study role mTOR regulation system, we investigated (immuno)proteasome expression during epileptogenesis, as well effects inhibitor rapamycin.The constitutive (β1, β5) and immunoproteasome (β1i, β5i) subunits was using immunohistochemistry electrical post-status epilepticus (SE) rat model for...
Tuberous sclerosis complex (TSC), a rare genetic disorder caused by mutation in the TSC1 or TSC2 gene, is characterized growth of hamartomas several organs. This includes low-grade brain tumors, known as subependymal giant cell astrocytomas (SEGA). Previous studies have shown differential expression genes related to extracellular matrix SEGA. Matrix metalloproteinases (MMPs), and their tissue inhibitors (TIMPs) are responsible for remodeling associated with tumorigenesis. study aimed...
Abstract Background The genetic disorder tuberous sclerosis complex (TSC) is frequently accompanied by the development of neuropsychiatric disorders, including autism spectrum and intellectual disability, with varying degrees impairment. These co-morbidities in TSC have been linked to structural brain abnormalities, such as cortical tubers, recurrent epileptic seizures (in 70–80% cases). Previous transcriptomic analysis tubers revealed dysregulation genes involved cell adhesion brain, which...
Tuberous sclerosis complex (TSC) is a genetic disorder associated with dysregulation of the mechanistic target rapamycin 1 (mTORC1) signalling pathway. Neurodevelopmental disorders, frequently present in TSC, are linked to cortical tubers brain. We previously reported microRNA-34a (miR-34a) among most upregulated miRs tubers. Here, we characterised miR-34a expression focus on early brain development and assessed regulation mTORC1 pathway corticogenesis by miR-34a.
Drug-resistant epilepsy patients may benefit from non-pharmacological therapies, such as the ketogenic diet (KD). However, its high fat content poses compliance challenges and metabolic risks. To mitigate this, we developed a novel KD composition with less additional nutrients (citrate, nicotinamide riboside, omega-3 fatty acids) for ketone-independent neuroprotection. The efficacy, neuropathological effects of classic were compared to control in rapid kindling model temporal lobe epilepsy....
Abstract Background Heterogeneity in the progression of clinical dementia poses a significant challenge, impeding effectiveness current therapies for Alzheimer’s disease (AD). To decipher molecular mechanisms governing heterogeneity AD that remains critical knowledge gap precluding rational therapeutic design, we investigated biochemical and biophysical properties tau present inferior temporal gyrus (ITG) prefrontal cortex (PFC) brain regions patients who had varying rates. explore gene...