Abstract:
:The lysosomal lumen contains numerous acidic hydrolases involved in the degradation of carbohydrates, lipids, proteins, and nucleic acids, which are basic cell components that turn over continuously within the cell and/or are ingested from outside of the cell. Deficiency in almost any of these hydrolases causes accumulation of the undigested material in secondary lysosomes, which manifests itself as a form of lysosomal storage disorder (LSD). Mutations in tripeptidyl-peptidase I (TPP I) underlie the classic late-infantile form of neuronal ceroid lipofuscinoses (CLN2), the most common neurodegenerative disorders of childhood. TPP I is an aminopeptidase with minor endopeptidase activity and Ser475 serving as an active-site nucleophile. The enzyme is synthesized as a highly glycosylated precursor transported by mannose-6-phosphate receptors to lysosomes, where it undergoes proteolytic maturation. This review summarizes recent progress in understanding of TPP I biology and molecular pathology of the CLN2 disease process, including distribution of the enzyme, its biosynthesis, glycosylation, transport and activation, as well as catalytic mechanisms and their potential implications for pathogenesis and treatment of the underlying disease. Promising data from gene and stem cell therapy in laboratory animals raise hope that CLN2 will be the first neurodegenerative LSD for which causative treatment will become available for humans.
journal_name
Biol Chemjournal_title
Biological chemistryauthors
Golabek AA,Kida Edoi
10.1515/BC.2006.135subject
Has Abstractpub_date
2006-08-01 00:00:00pages
1091-9issue
8eissn
1431-6730issn
1437-4315journal_volume
387pub_type
杂志文章,评审abstract::Abstract Hairpin ribozymes occur naturally only in the satellite RNAs of tobacco ringspot virus (TRsV), chicory yellow mottle virus (CYMoV) and arabis mosaic virus (ArMV). The catalytic centre of the predominantly studied sTRsV hairpin ribozyme, and of sArMV is organised around a four-way helical junction. We show her...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2011.071
更新日期:2011-07-01 00:00:00
abstract::Extreme thermophiles produce unusually long polyamines, including the linear caldopentamine (Cdp) and the branched pentamine tetrakis(3-aminopropyl)-ammonium (Taa), with the latter containing a central quaternary ammonium moiety. Here we compare the interaction of these two pentamines with RNA by studying the heat den...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2009.096
更新日期:2009-09-01 00:00:00
abstract::Abstract The homeostasis and atheroprotective function of bilirubin could be an appealing model to investigate one of the many physiologic functions of the human aryl hydrocarbon receptor (AhR). Several clinical and epidemiological studies have been carried out on key enzymes generating and eliminating bilirubin (heme...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2010.065
更新日期:2010-06-01 00:00:00
abstract::A large number of prostate cancer (PCa) patients receive treatment without significant benefits, strengthening the need for accurate prognosis, which can be supported by the study of miRNAs. In silico specificity analysis was performed for the identification of miRNAs able to regulate KLK2 and KLK4 expression. Total R...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2014-0150
更新日期:2014-09-01 00:00:00
abstract::Silver nanoparticles (AgNPs) have many biological applications in biomedicine, biotechnology and other life sciences. Depending on the size, shape and the type of carrier, AgNPs demonstrate different physical and chemical properties. AgNPs have strong antimicrobial, antiviral and antifungal activity, thus they are use...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2012-0202
更新日期:2013-01-01 00:00:00
abstract::The adipocytokine adiponectin and its receptor (AdipoR) comprise a new receptor-ligand system that is involved in a variety of clinically important morbidities such as obesity, type 2 diabetes and cardiovascular diseases. Adiponectin exerts a multitude of beneficial and tissue specific effects depending on its unique,...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2010.104
更新日期:2010-09-01 00:00:00
abstract::The neurobiological mechanisms of obesity-induced peripheral neuropathy are poorly understood. We evaluated the role of Sigma-1 receptor (Sig-1R) and NMDA receptor (NMDARs) in the spinal cord in peripheral neuropathy using an animal model of high fat diet-induced diabetes. We examined the expression of Sig-1R and NMDA...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2017-0117
更新日期:2017-09-26 00:00:00
abstract::The purpose of this work was to study the regulative role of the glutamate receptor found earlier in the brain mitochondria. In the present work a glutamate-dependent signaling system with similar features was detected in mitochondria of the heart. The glutamate-dependent signaling system in the heart mitochondria was...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2015-0289
更新日期:2016-05-01 00:00:00
abstract::Cytokinins are essential plant hormones that regulate numerous physiological processes. Recently, a protein was identified in mung bean (Vigna radiata) and characterized as a cytokinin-specific binding protein (VrCSBP). Fluorescence correlation spectroscopy was used to investigate the interaction between VrCSBP and it...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2010.005
更新日期:2010-01-01 00:00:00
abstract::Gaucher disease (GD) is a lysosomal storage disorder, caused by an impaired function of β-glucocerebrosidase, which results in accumulation of glucocerebroside in cells, and altered membrane ordering. Using electron paramagnetic resonance spin labeling, a statistically significant difference in the order parameter bet...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2017-0241
更新日期:2018-04-25 00:00:00
abstract::The T-knot scaffold, a disulphide-reinforced structural motif shared by several proteins with very different biological functions, has been defined as 'a stretch of the protein chain which comprises two strands of a beta-sheet and three loops, knotted by two disulphides into the shape of the letter T'. In this communi...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.1999.159
更新日期:1999-10-01 00:00:00
abstract::TNF-alpha is a major pro-inflammatory cytokine that regulates further cytokine induction, especially of IL-1 and IL-6, in many human diseases including cancer, inflammation and immune disorders. In a search for new inhibitors of inducible TNF-alpha promoter activity and expression, cultures of the imperfect fungus Tri...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2007.066
更新日期:2007-06-01 00:00:00
abstract::In preeclampsia and hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome, impaired trophoblast invasion and excessive fibrin deposition in the placental intervillous space is associated with fetal compromise. However, little information is available whether modulation of placental protease expression--p...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2009.123
更新日期:2009-11-01 00:00:00
abstract::Induction of apoptosis by selective BH3-mimetics is currently investigated as a novel strategy for cancer treatment. Here, we report that selective BH3-mimetics induce apoptosis in a variety of hematological malignancies. Apoptosis is accompanied by severe mitochondrial toxicities upstream of caspase activation. Speci...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2018-0233
更新日期:2019-01-28 00:00:00
abstract::Calpain is a calcium-activated non lysosomal neutral thiol protease (EC 3.4.22.17) present in a wide variety of eukaryotic cells. Calpain is usually present as an inactive form and is activated by calcium ions and phospholipids. The ability of calpain to alter, by limited proteolysis, the activity or function of numer...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2002.079
更新日期:2002-05-01 00:00:00
abstract::The occurrence of rhodanese-like proteins in the major evolutionary phyla, together with the observed abundance of these proteins also within the same genome, suggests that their function cannot be limited to cyanide scavenging. The aim of the present study was to investigate whether Azotobacter vinelandii RhdA, an en...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2003.163
更新日期:2003-10-01 00:00:00
abstract::Malaria can be a very severe disease, particularly in young children, pregnant women (mostly in primipara), and malaria naïve adults, and currently ranks among the most prevalent infections in tropical and subtropical areas throughout the world. The widespread occurrence and the increased incidence of malaria in many ...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2001.069
更新日期:2001-04-01 00:00:00
abstract::Lipids serve many distinct functions in cellular homeostasis such as membrane organization, as a platform for membrane function and protein/protein or protein/lipid interaction, energy storage, as well as secondary messengers in signal transduction. Perturbations in lipid homeostasis may result in abnormal cellular fu...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/hsz-2015-0207
更新日期:2015-12-01 00:00:00
abstract::The kinin B2 receptor, which is constitutively expressed in a large number of tissues, mediates most of the known effects of bradykinin (BK). Normally undetectable in healthy tissues, the B1 receptor is strongly over-expressed under pathological conditions. BK is an important mediator in renal homeostasis and is mainl...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2006.004
更新日期:2006-01-01 00:00:00
abstract::As the outermost barrier of the body, the skin is directly and frequently exposed to a prooxidative environment, including solar UVA and UVB radiation, and air pollution. Ozone, a major air pollutant, possesses a strong oxidizing potential and therefore is possibly one of the most reactive chemicals the skin ever meet...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/bchm.1997.378.11.1299
更新日期:1997-11-01 00:00:00
abstract::The main function of the epidermis is to establish a vital multifunctional barrier between the body and its external environment. A defective epidermal barrier is one of the key features of atopic dermatitis (AD), a chronic and relapsing inflammatory skin disorder that affects up to 20% of children and 2-3% of adults ...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/hsz-2015-0141
更新日期:2015-11-01 00:00:00
abstract::Myocardial zinc dyshomeostasis is associated with caspase-3 activation, ErbB2 degradation and apoptosis during hypoxia/reoxygenation. Zinc pyrithione replenishes intracellular zinc, suppresses caspase-3, augments ErbB2 levels and improves cell survival. We hypothesize that zinc is capable of modulating redox and endop...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2020-0167
更新日期:2020-10-25 00:00:00
abstract::The formation of reactive oxygen species (ROS) can be induced by xenobiotic substances, such as redox cycling molecules, but also by endogenous substances such as hormones and cytokines. Recent research shows the importance of ROS in cellular signaling. Here, the signaling pathways of the two blood pressure-regulating...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2010.136
更新日期:2010-11-01 00:00:00
abstract::Stromal cell-derived factor-1alpha (SDF-1alpha) is a strong migratory stimulant for hematopoietic stem and progenitor cells (HSPCs). The hematopoietic cytokines thrombopoietin (TPO), Flt3-ligand (FL), stem cell factor (SCF) and interleukin 11 (IL-11) are able to stimulate amplification of primitive murine hematopoieti...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2008.099
更新日期:2008-07-01 00:00:00
abstract::The enzyme L-asparaginase is a crucial component in the treatment of acute lymphoblastic leukemia (ALL). As all asparaginases in clinical use are derived from microorganisms, immunological reactions are the most important adverse events associated with asparaginase treatment. Two different methods, phage display and t...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2005.063
更新日期:2005-06-01 00:00:00
abstract::Characterization of protein damage during photosensitization of chlorin e6-treated cells was performed using the green fluorescent protein (GFP). The GFP-chromophore damage caused by singlet oxygen was studied in COS 7 kidney cells and E. coli bacteria following light irradiation. Electron spin resonance (ESR) reveale...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2000.153
更新日期:2000-12-01 00:00:00
abstract::A high-resolution crystallographic structure determination of a protein-ligand complex is generally accepted as the 'gold standard' for structure-based drug design, yet the relationship between structure and affinity is neither obvious nor straightforward. Here we analyze the interactions of a series of serine protein...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2014-0158
更新日期:2014-07-01 00:00:00
abstract::Glutaminyl cyclases (QC) catalyze the intramolecular cyclization of N-terminal glutamine residues of peptides and proteins. For a comparison of the substrate specificity of human and papaya QC enzymes, a novel continuous assay was established by adapting an existing discontinuous method. Specificity constants (kcat/Km...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2003.175
更新日期:2003-12-01 00:00:00
abstract::The molecular architectures of the catalytic core of protein phosphatase 1 (PP1) and protein phosphatase 2B (PP2B) are similar, and both contain a beta12-beta13 loop that consists of non-conserved residues. A truncation mutant containing the PP2B catalytic domain has previously been constructed in our laboratory, and ...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2006.183
更新日期:2006-10-01 00:00:00
abstract::The conversion of the cellular isoform of the prion protein (PrP(C)) into the pathologic isoform (PrP(Sc)) is the key event in prion diseases. To study the conversion process, an in vitro system based on varying the concentration of low amounts of sodium dodecyl sulfate (SDS) has been employed. In the present study, t...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2011.048
更新日期:2011-05-01 00:00:00