A5024877991- Alzheimer's disease research and treatments
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Neuroinflammation and Neurodegeneration Mechanisms
- Cellular transport and secretion
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Cholinesterase and Neurodegenerative Diseases
- Prion Diseases and Protein Misfolding
- Genetic Neurodegenerative Diseases
- Pancreatic function and diabetes
- RNA modifications and cancer
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Amino Acid Enzymes and Metabolism
- Tryptophan and brain disorders
- Supramolecular Self-Assembly in Materials
- Protein Structure and Dynamics
- Amyotrophic Lateral Sclerosis Research
- Neurogenesis and neuroplasticity mechanisms
- S100 Proteins and Annexins
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Lysosomal Storage Disorders Research
- Trace Elements in Health
Amsterdam Neuroscience
2009-2024
Vrije Universiteit Amsterdam
2014-2024
Amsterdam University Medical Centers
2019-2024
Creative Commons
2023
Utrecht University
1994-2019
University Medical Center Utrecht
2019
Amsterdam UMC Location University of Amsterdam
2006-2017
Amsterdam UMC Location Vrije Universiteit Amsterdam
2013-2017
University of Amsterdam
2005-2017
Mario Negri Institute for Pharmacological Research
2010
The unfolded protein response (UPR) is a stress activated upon disturbed homeostasis in the endoplasmic reticulum (ER). Previously, we reported that activation of UPR closely correlates with presence phosphorylated tau (p-tau) Alzheimer's disease (AD). As well as increased intracellular p-tau, AD brains are characterized by extracellular deposits β amyloid (Aβ). Recent vitro studies have shown Aβ can induce ER and UPR. aim present study to investigate sporadic tauopathies like progressive...
We have demonstrated that the polyethylene glycol (PEG) corona of long-circulating polymeric nanoparticles (NPs) favors interaction with amyloid-beta (Aβ(1-42)) peptide both in solution and serum. The influence PEGylation poly(alkyl cyanoacrylate) poly(lactic acid) NPs on monomeric soluble oligomeric forms Aβ(1-42) was by capillary electrophoresis, surface plasmon resonance, thioflavin T assay, confocal microscopy, where binding affected aggregation kinetics. capture serum also evidenced...
A versatile and efficient functionalization strategy for polymeric nanoparticles (NPs) has been reported successfully applied to PEGylated, biodegradable poly(alkyl cyanoacrylate) (PACA) nanocarriers. The relevance of this platform was demonstrated in both the fields cancer Alzheimer's disease (AD). Prepared by copper-catalyzed azide–alkyne cycloaddition (CuAAC) subsequent self-assembly aqueous solution amphiphilic copolymers, resulting functionalized NPs exhibited requisite characteristics...
The recent generation of induced pluripotent stem cells (iPSCs) from a patient with Parkinson's disease (PD) resulting triplication the α-synuclein (SNCA) gene locus allows unprecedented opportunities to explore its contribution molecular pathogenesis PD. We used double-nicking CRISPR/Cas9 system conduct site-specific mutagenesis SNCA in these cells, generating an isogenic iPSC line normalized dosage. Comparative expression analysis neuronal derivatives iPSCs revealed ER stress phenotype,...
The mechanism of synaptic loss in Alzheimer's disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional pathology ([18F]flortaucipir PET), density (synaptic vesicle 2A [11C]UCB-J PET) function disease.Seven amyloid-positive subjects from the Amsterdam Dementia Cohort underwent dynamic 130-min [18F]flortaucipir PET, 60-min PET...
Abstract The key pathogenic event in the onset of Alzheimer's disease (AD) is aggregation β‐amyloid (Aβ) peptides into toxic aggregates. Molecules that interfere with this process might act as therapeutic agents for treatment AD. amino acid residues 16–20 (KLVFF) are known to be essential Aβ. In study, we have used a first‐generation dendrimer scaffold multivalent display KLVFF peptide. effect four attached (K 4 ) on Aβ was compared monomeric 1 ). Our data show K very effectively inhibits...
Protein folding stress in the endoplasmic reticulum (ER) may lead to activation of unfolded protein response (UPR), aimed restore proteostasis ER. Previously, we demonstrated that UPR is an early event Alzheimer disease (AD) brain. In our recent work investigated whether employed enhance capacity ubiquitin proteasome system or autophagy neuronal cells. We showed levels, composition and activity are not regulated by UPR. contrast, enhances LC3 levels increased neurons displaying AD Our data...
The unfolded protein response (UPR) is activated in neurodegenerative tauopathies such as Alzheimer's disease (AD) close connection with early stages of tau pathology. Metabolic disturbances are strongly associated increased risk for AD and a potent inducer the UPR. Here, we demonstrate that metabolic stress induces phosphorylation endogenous via activation Strikingly, upon restoration homeostasis, not only levels UPR markers pPERK, pIRE1α BiP, but also reversed both cell models well torpor,...
Granulovacuolar degeneration bodies (GVBs) are membrane-bound vacuolar structures harboring a dense core that accumulate in the brains of patients with neurodegenerative disorders, including Alzheimer's disease and other tauopathies. Insight into origin GVBs their connection to tau pathology has been limited by lack suitable experimental models for GVB formation. Here, we used confocal, automated, super-resolution electron microscopy demonstrate seeding triggers formation different mouse...
The terminal stages of neuronal degeneration and death in neurodegenerative diseases remain elusive. Autophagy is an essential catabolic process frequently failing neurodegeneration. Selective autophagy routes have recently emerged, including nucleophagy, defined as degradation nuclear components by autophagy. Here, we show that, a mouse model for the polyglutamine disease dentatorubral-pallidoluysian atrophy (DRPLA), progressive acquirement ataxic phenotype linked to severe cerebellar...
Alzheimer's disease (AD) is characterized by the aggregation of misfolded proteins. Previously we reported activation unfolded protein response (UPR) in AD neurons. A potential source for UPR neurons may be increased levels beta-amyloid (Abeta). In this study, used preparations enriched oligomeric or fibrillar Abeta (1-42) to investigate role conformational state differentiated neuroblastoma cells. Both and do not induce BiP expression extent that it can detected a pool However, using...