A5006229965- Alzheimer's disease research and treatments
- Lysosomal Storage Disorders Research
- Genetics and Neurodevelopmental Disorders
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Neuroinflammation and Neurodegeneration Mechanisms
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Lipid Membrane Structure and Behavior
- Metabolomics and Mass Spectrometry Studies
- Cystic Fibrosis Research Advances
- Infant Nutrition and Health
- RNA regulation and disease
- Synthesis of β-Lactam Compounds
- Ubiquitin and proteasome pathways
- Genomic variations and chromosomal abnormalities
- Crystallography and molecular interactions
- Parkinson's Disease Mechanisms and Treatments
- Crystallization and Solubility Studies
- RNA modifications and cancer
- Tryptophan and brain disorders
- Nuclear Receptors and Signaling
- X-ray Diffraction in Crystallography
- Autism Spectrum Disorder Research
- Muscle Physiology and Disorders
Rudjer Boskovic Institute
2013-2023
Croatian Institute of Transfusion Medicine
2010
Washington University in St. Louis
2004
United States Military Academy
2003
MSD K.K. (Japan)
2003
The University of Tokyo
2003
Notch receptors and the amyloid precursor protein are type I membrane proteins that proteolytically cleaved within their transmembrane domains by a presenilin (PS)-dependent γ-secretase activity. In both proteins, two peptide bonds hydrolyzed: one near inner leaflet other in middle of domain. Under saturating conditions substrates compete with each for proteolysis, but not binding to PS. At least some Alzheimer's disease-causing PS mutations reside possessing low catalytic We demonstrate ( i...
Proper function of lysosomes is particularly important in neurons, as they cannot dilute accumulated toxic molecules and aggregates by cell division. Thus, impairment lysosomal plays an role neuronal degeneration the pathogenesis numerous neurodegenerative diseases. In this work we analyzed how inhibition and/or loss major proteases, cysteine cathepsins B L (CtsB/L), affects function, cholesterol metabolism degradation key Alzheimer's disease (AD) proteins. Here, show that CtsB/L, not...
Abstract Niemann-Pick type C disease is a rare neurodegenerative disorder mainly caused by mutations in NPC1 , resulting abnormal late endosomal/lysosomal lipid storage. Although microgliosis prominent pathological feature, direct consequences of loss on microglial function remain not fully characterized. We discovered proteomic signatures and phenotypes NPC1-deficient murine models demonstrate cell autonomous microglia. Loss triggers enhanced phagocytic uptake impaired myelin turnover...
The low density lipoprotein (LDL) receptor-related protein 1B (LRP1B) is a newly identified member of the LDL receptor family that shares high homology with (LRP). LRP1B was originally described as putative tumor suppressor in lung cancer cells; however, its expression profile several regions adult human brain suggests it may have additional functions central nervous system. Since has overlapping ligand binding properties LRP, we investigated whether LRP1B, like could interact beta-amyloid...
Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also a seemingly distinct Niemann-Pick type C with primarily juvenile-onset. This strongly argues for an overlap pathogenic mechanisms. The commonly researched include various cell subsets microglia, peripheral macrophages, or regulatory T cells...
Increasing evidence implicates lysosomal dysfunction in the pathogenesis of neurodegenerative diseases, including rare inherited storage disorders (LSDs) and most common such as Alzheimer's Parkinson's disease (AD PD). Although triggers impairment may involve accumulated macromolecules or enzymes, role glycocalyx (dys)function has not been studied. The goal this work was to analyze whether there are changes a cellular model LSD Niemann-Pick type C (NPC). Using ferrofluid nanoparticles we...
Impaired lysosomal activity, which results in defective protein processing, waste accumulation, and aggregation, is implicated a number of disease pathologies. Acidification lysosomes crucial process required for lysosome function. Previously we showed that inhibition glycogen synthase kinase-3 (GSK-3) enhanced acidification both normal pathological conditions. However, how GSK-3 integrates into the networking unknown. Here show mTORC1 increased autophagic activity are downstream to...
Fragile X mutation detection by DNA analysis enables accurate diagnosis of the fragile syndrome. The involves expansion CGG repeats in FMR1 gene and has been primarily detected Southern blotting method. In this study we present a novel, efficient reliable PCR protocol that is more convenient for routine This method based on use Expand Long System, which amplification normal, premutated full-mutated alleles, therefore provides complete repeat gene. Normal alleles were easily ethidium bromide...
Niemann-Pick type C (NPC) disease, sometimes called childhood Alzheimer's, is a rare neurovisceral lipid storage disease with progressive neurodegeneration leading to premature death. The caused by loss-of-function mutations in the Npc1 or Npc2 gene which both result into accumulation late endosomes and lysosomes. Since presents broad heterogenous clinical spectrum, involved mechanisms are still incompletely understood this hampers finding an effective treatment. As NPC patients, who carry...
Two new trans-(3R,4R)-amino-β-lactam derivatives and their diastereoisomeric mixtures were synthesized as ezetimibe bioisosteres tested in vitro vivo experiments novel β-lactam cholesterol absorption inhibitors. Both compounds exhibited low cytotoxicity MDCKII, hNPC1L1/MDCKII, HepG2 cell lines potent inhibitory effect hNPC1L1/MDCKII cells. In addition, these markedly reduced mice, resulting concentrations plasma, liver, intestine. We determined the crystal structure of one amino-β-lactam...
The β-lactam cholesterol absorption inhibitor ezetimibe is so far the only representative of this class compounds on market today. goal work was to synthesize new amide analogs from trans-3-amino-(3R,4R)-β-lactam and test their cytotoxicity activity as inhibitors. We synthesized six analogs. All exhibited low toxicity in MDCKIIwt, hNPC1L1/MDCKII HepG2 cell lines showed significant inhibition uptake cells. In addition, we determined three inhibit vivo. Our results demonstrate that these...