A5036137834- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Calcium signaling and nucleotide metabolism
- Ubiquitin and proteasome pathways
- Connective tissue disorders research
- Glycogen Storage Diseases and Myoclonus
- Vitamin D Research Studies
- Bone Metabolism and Diseases
- Carbohydrate Chemistry and Synthesis
- Protein Kinase Regulation and GTPase Signaling
- Transgenic Plants and Applications
- Protease and Inhibitor Mechanisms
- Adenosine and Purinergic Signaling
- Endoplasmic Reticulum Stress and Disease
- Alkaline Phosphatase Research Studies
- Autophagy in Disease and Therapy
- Retinal Development and Disorders
- Biochemical Acid Research Studies
- Cancer-related gene regulation
- Plant tissue culture and regeneration
Universität Hamburg
2018-2023
University Medical Center Hamburg-Eppendorf
2018-2023
Defects in the MFSD8 gene encoding lysosomal membrane protein CLN7 lead to disease, a neurodegenerative storage disorder belonging group of neuronal ceroid lipofuscinoses. Here, we have performed SILAC-based quantitative analysis proteome using Cln7-deficient mouse embryonic fibroblasts (MEFs) from Cln7 knockout (ko) model. From 3335 different proteins identified, detected 56 soluble and 29 highly abundant proteins. Quantification revealed that amounts 12 were significantly reduced ko MEFs...
Mutations in the GNPTAB and GNPTG genes cause mucolipidosis (ML) type II, III alpha/beta, gamma, which are autosomal recessively inherited lysosomal storage disorders. encode α/β-precursor γ-subunit of N-acetylglucosamine (GlcNAc)-1-phosphotransferase, respectively, key enzyme for generation mannose 6-phosphate targeting signals on enzymes. Defective GlcNAc-1-phosphotransferase results missorting enzymes accumulation non-degradable macromolecules lysosomes, strongly impairing cellular...
Abstract Neuronal ceroid lipofuscinosis (NCL) type 1 (CLN1) is a neurodegenerative storage disorder caused by mutations in the gene encoding lysosomal enzyme palmitoyl-protein thioesterase (PPT1). CLN1 patients suffer from brain atrophy, mental and motor retardation, seizures, retinal degeneration ultimately resulting blindness. Here, we performed an in-depth analysis of phenotype PPT1-deficient mouse, animal model this condition. Reactive astrogliosis microgliosis were evident mutant...
Abstract Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal growth. In present study, we treated them weekly injection recombinant human ARSB (rhARSB) to analyze impact replacement therapy (ERT) on growth remodeling. found all...
Significance Statement Patients with the severe lysosomal storage disorder mucolipidosis II (MLII) have mild microalbuminuria, among other symptoms, but patients milder MLIII do not proteinuria. Both conditions result from mutations in same gene. Mouse models of each reveal that distinct mechanisms compensate for disruption protein synthesis balance glomeruli. MLII and downregulate complex mTORC1 (mammalian target rapamycin 1) signaling to dampen synthesis, also increases integrated stress...
ABSTRACT Mucolipidosis type III (MLIII) gamma is a rare inherited lysosomal storage disorder caused by mutations in GNPTG encoding the γ-subunit of GlcNAc-1-phosphotransferase, key enzyme ensuring proper intracellular location multiple enzymes. Patients with MLIII typically present osteoarthritis and joint stiffness, suggesting cartilage involvement. Using Gnptg knockout (Gnptgko) mice as model human disease, we showed that missorting number enzymes associated accumulation chondroitin...
BNIP1 (BCL2 interacting protein 1) is a soluble N-ethylmaleimide-sensitive factor-attachment receptor involved in ER membrane fusion. We identified the homozygous intronic variant c.84+3A>T apparently unrelated patients 1 and 2 with disproportionate short stature. Radiographs showed abnormalities affecting both axial appendicular skeleton spondylo-epiphyseal dysplasia. detected ~80% aberrantly spliced pre-mRNAs, reduced mRNA level to ~80%, reduction by ~50% patient compared control...
Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans lysosomes. Costly enzyme replacement therapy (ERT) the conventional treatment for MPS I. Toward producing more cost-effective and safe alternative to commercial mammalian cell-based production systems, we have produced recombinant human IDUA seeds an Arabidopsis mutant generate biologically active non-immunogenic...
Mucolipidosis (ML) II and III alpha/beta are inherited lysosomal storage disorders caused by mutations in GNPTAB encoding the α/β-precursor of GlcNAc-1-phosphotransferase. This enzyme catalyzes initial step modification more than 70 enzymes with mannose 6-phosphate residues to ensure their intracellular targeting lysosomes. The so-called stealth domains α- β-subunit GlcNAc-1-phosphotransferase were thought be involved substrate recognition and/or catalysis. Here, we performed silico...
Pathogenic variants in GNPTAB and GNPTG, encoding different subunits of GlcNAc-1-phosphotransferase, cause mucolipidosis (ML) II, MLIII alpha/beta, gamma. This study aimed to investigate the cellular molecular bases underlying skeletal abnormalities patients with MLII MLIII.We analyzed bone biopsies from alpha/beta or gamma by undecalcified histology histomorphometry. The status Gnptgko Gnptab-deficient mice was determined complemented biochemical analysis primary cells. clinical relevance...
Severe skeletal alterations are common symptoms in patients with mucolipidosis type II (MLII), a rare lysosomal storage disorder of childhood. We have previously reported that progressive bone loss mouse model for MLII is caused by an increased number bone-resorbing osteoclasts, which accompanied elevated expression the cytokine interleukin-6 (IL-6) microenvironment. In present study we addressed question, if pharmacological blockade IL-6 can prevent low mass phenotype mice. Since cellular...