aspartic acid endopeptidases

Summary

Summary: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.

Top Publications

  1. Yuksel M, Biberoglu K, Onder S, Akbulut K, Tacal O. Effects of phenothiazine-structured compounds on APP processing in Alzheimer's disease cellular model. Biochimie. 2017;138:82-89 pubmed publisher
    ..Taken together, our results represent the first report demonstrating that TBO and TH can affect amyloid metabolism in vitro. ..
  2. Custovic A, Green R, Taggart S, Smith A, Pickering C, Chapman M, et al. Domestic allergens in public places. II: Dog (Can f1) and cockroach (Bla g 2) allergens in dust and mite, cat, dog and cockroach allergens in the air in public buildings. Clin Exp Allergy. 1996;26:1246-52 pubmed
    ..Exposure to cockroach allergens in schools may be important for cockroach sensitized asthmatic children. ..
  3. Yan G, Hao L, Niu Y, Huang W, Wang W, Xu F, et al. 2-Substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamides as BACE1 inhibitors: Synthesis, biological evaluation and docking studies. Eur J Med Chem. 2017;137:462-475 pubmed publisher
    ..The studies revealed that the most potent analog 41 (IC50 = 4.6 ?M) with high predicted BBB permeability and low cellular cytotoxicity, could serve as a good lead structure for further optimization. ..
  4. Kumar R, Saraswat D, Tati S, Edgerton M. Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis. Infect Immun. 2015;83:2614-26 pubmed
    ..Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis. ..
  5. Tomita S, Kirino Y, Suzuki T. Cleavage of Alzheimer's amyloid precursor protein (APP) by secretases occurs after O-glycosylation of APP in the protein secretory pathway. Identification of intracellular compartments in which APP cleavage occurs without using toxic agents that inte. J Biol Chem. 1998;273:6277-84 pubmed
  6. Sachdev D, Chirgwin J. Order of fusions between bacterial and mammalian proteins can determine solubility in Escherichia coli. Biochem Biophys Res Commun. 1998;244:933-7 pubmed
    ..Thus, inclusion body formation may be the consequence, rather than the cause, of non-native folding in vivo, and in E. coli soluble proteins may fold into states different from those reached in vitro. ..
  7. Nakagomi S, Kiryu Seo S, Kiyama H. Endothelin-converting enzymes and endothelin receptor B messenger RNAs are expressed in different neural cell species and these messenger RNAs are coordinately induced in neurons and astrocytes respectively following nerve injury. Neuroscience. 2000;101:441-9 pubmed
  8. Citron M, Teplow D, Selkoe D. Generation of amyloid beta protein from its precursor is sequence specific. Neuron. 1995;14:661-70 pubmed
    ..Our results have important implications for current intensive approaches to develop assays for and identify enzymes with beta-secretase activity. ..
  9. Turturice B, Ranjan R, Nguyen B, Hughes L, Andropolis K, Gold D, et al. Perinatal Bacterial Exposure Contributes to IL-13 Aeroallergen Response. Am J Respir Cell Mol Biol. 2017;57:419-427 pubmed publisher
    ..Together, these results underscore the relationship between immune responses to allergens and bacterial exposure during perinatal development. ..

More Information

Publications58

  1. Schneppenheim J, Loock A, Hüttl S, Schweizer M, Lüllmann Rauch R, Oberg H, et al. The Influence of MHC Class II on B Cell Defects Induced by Invariant Chain/CD74 N-Terminal Fragments. J Immunol. 2017;199:172-185 pubmed publisher
    ..In addition, different functional properties of the longer, MHCII-bound CD74 NTF could contribute to the milder phenotype of CatS-/- B cells. ..
  2. Kido Nakahara M, Buddenkotte J, Kempkes C, Ikoma A, Cevikbas F, Akiyama T, et al. Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus. J Clin Invest. 2014;124:2683-95 pubmed publisher
    ..Furthermore, these results implicate the ET-1/ECE-1/ERK1/2 pathway as a therapeutic target to treat pruritus in humans. ..
  3. Bernstein H, Lendeckel U, Steiner J, Bogerts B. Oestrogen downregulates BACE protein in human cell culture: what does this teach us about Alzheimer's disease?. Neurodegener Dis. 2011;8:153-4 pubmed publisher
  4. Haghighijoo Z, Firuzi O, Hemmateenejad B, Emami S, Edraki N, Miri R. Synthesis and biological evaluation of quinazolinone-based hydrazones with potential use in Alzheimer's disease. Bioorg Chem. 2017;74:126-133 pubmed publisher
    ..These results demonstrate that quinazolinone-hydrazone derivatives represent a valuable scaffold for the discovery of novel non-peptidic BACE1 inhibitors. ..
  5. Sachdev D, Chirgwin J. Properties of soluble fusions between mammalian aspartic proteinases and bacterial maltose-binding protein. J Protein Chem. 1999;18:127-36 pubmed
    ..The results suggest that MBP-aspartic proteinase fusions can provide a source of soluble but nonnative folding states of the mammalian polypeptides in the absence of aggregation. ..
  6. Cooper J, Quail W, Frazao C, Foundling S, Blundell T, Humblet C, et al. X-ray crystallographic analysis of inhibition of endothiapepsin by cyclohexyl renin inhibitors. Biochemistry. 1992;31:8142-50 pubmed
    ..The relative potencies of PD125967 and PD125754 for endothiapepsin are consistent with the changes in solvent-accessible area which take place on inhibitor binding. ..
  7. Du X, Huo X, Yang Y, Hu Z, Botchway B, Jiang Y, et al. miR-124 downregulates BACE 1 and alters autophagy in APP/PS1 transgenic mice. Toxicol Lett. 2017;280:195-205 pubmed publisher
    ..In view of this, we hypothesis that miR-124 conducts its neuroprotective effect through BACE 1 by regulation of autophagic pathways. ..
  8. Huang J, Sun B, Yao Y, Liu J. Fast and Reliable Thermodynamic Approach for Determining the Protonation State of the Asp Dyad. J Chem Inf Model. 2017;57:2273-2280 pubmed publisher
    ..It is clear that our thermodynamic approach could be used to rapidly and reliably determine the protonation state of the asp dyad. ..
  9. Zhao X, Gong D, Jiang Y, Guo D, Zhu Y, Deng Y. Multipotent AChE and BACE-1 inhibitors for the treatment of Alzheimer's disease: Design, synthesis and bio-analysis of 7-amino-1,4-dihydro-2H-isoquilin-3-one derivates. Eur J Med Chem. 2017;138:738-747 pubmed publisher
    ..68 ± 8.01% at 20 ?M), and good metal chelating property, which can be chosen as lead compound for further optimization of novel small ligand for the treatment of Alzheimer's disease. ..
  10. Tempel W, Wu H, Dombrovsky L, Zeng H, Loppnau P, Zhu H, et al. An intact SAM-dependent methyltransferase fold is encoded by the human endothelin-converting enzyme-2 gene. Proteins. 2009;74:789-93 pubmed publisher
  11. Azimi S, Zonouzi A, Firuzi O, Iraji A, Saeedi M, Mahdavi M, et al. Discovery of imidazopyridines containing isoindoline-1,3-dione framework as a new class of BACE1 inhibitors: Design, synthesis and SAR analysis. Eur J Med Chem. 2017;138:729-737 pubmed publisher
    ..These findings demonstrate that imidazopyridines-based compounds bearing phthalimide moiety have the potential to decrease amyloid-? levels and ameliorate the symptoms of Alzheimer's disease. ..
  12. Kulas J, Puig K, Combs C. Amyloid precursor protein in pancreatic islets. J Endocrinol. 2017;235:49-67 pubmed publisher
    ..We conclude that APP and its metabolites are capable of influencing the basic physiology of the pancreas, possibly through the release of sAPP acting in an autocrine or paracrine manner. ..
  13. Xie H, Zhao Y, Zhou Y, Liu L, Liu Y, Wang D, et al. MiR-9 Regulates the Expression of BACE1 in Dementia Induced by Chronic Brain Hypoperfusion in Rats. Cell Physiol Biochem. 2017;42:1213-1226 pubmed publisher
    ..We conclude that miR-9 plays an important role in regulating the process of dementia induced by 2VO in rats by increasing BACE1 expression via downregulation of CREB. ..
  14. Hartmann T, Bieger S, Brühl B, Tienari P, Ida N, Allsop D, et al. Distinct sites of intracellular production for Alzheimer's disease A beta40/42 amyloid peptides. Nat Med. 1997;3:1016-20 pubmed
    ..We suggest that the earliest event taking place in AD might be the generation of A beta(1-42) in the ER. ..
  15. Mastan B, Narwal S, Dey S, Kumar K, Mishra S. Plasmodium berghei plasmepsin VIII is essential for sporozoite gliding motility. Int J Parasitol. 2017;47:239-245 pubmed publisher
    ..By targeted gene deletion, we show that PbPM VIII is critical for sporozoite egress from an oocyst and gliding motility, which is a prerequisite for the invasion of salivary glands and subsequent transmission to the vertebrate host. ..
  16. Shi Z, Chen T, Yao Q, Zheng L, Zhang Z, Wang J, et al. The circular RNA ciRS-7 promotes APP and BACE1 degradation in an NF-?B-dependent manner. FEBS J. 2017;284:1096-1109 pubmed publisher
    ..Taken together, our data provide a molecular mechanism implicating reduced ciRS-7 expression in AD, suggesting that ciRS-7 may represent a useful target in the development of therapeutic strategies for AD. ..
  17. Pène V, Lemasson M, Harper F, Pierron G, Rosenberg A. Role of cleavage at the core-E1 junction of hepatitis C virus polyprotein in viral morphogenesis. PLoS ONE. 2017;12:e0175810 pubmed publisher
    ..Furthermore, capsid-containing particles did not accumulate in the absence of SP-catalyzed cleavage, suggesting the quality of newly formed viral particles is controlled before secretion. ..
  18. Agrawal S, Moser K, Morton L, Cummings M, Parihar A, Dwivedi A, et al. Association of a Novel Mutation in the Plasmodium falciparum Chloroquine Resistance Transporter With Decreased Piperaquine Sensitivity. J Infect Dis. 2017;216:468-476 pubmed publisher
    ..Our data suggest that, in addition to plasmepsin II/III copy number, other loci, including pfcrt, may also be involved in piperaquine resistance. ..
  19. Di Pietro O, Juárez Jiménez J, Muñoz Torrero D, Laughton C, Luque F. Unveiling a novel transient druggable pocket in BACE-1 through molecular simulations: Conformational analysis and binding mode of multisite inhibitors. PLoS ONE. 2017;12:e0177683 pubmed publisher
    ..Overall, these findings pave the way for the exploration of novel functionalities in the design of optimized BACE-1 multisite inhibitors. ..
  20. Maoz R, Garfinkel B, Soreq H. Alzheimer's Disease and ncRNAs. Adv Exp Med Biol. 2017;978:337-361 pubmed publisher
    ..Finally, we explore the potential promise of these findings for future therapeutic applications. ..
  21. Liebsch F, Aurousseau M, Bethge T, McGuire H, Scolari S, Herrmann A, et al. Full-length cellular ?-secretase has a trimeric subunit stoichiometry, and its sulfur-rich transmembrane interaction site modulates cytosolic copper compartmentalization. J Biol Chem. 2017;292:13258-13270 pubmed publisher
    ..In conclusion, therapeutic Alzheimer disease prevention strategies aimed at decreasing BACE1 protein levels should be regarded with caution, because adverse effects in copper homeostasis may occur. ..
  22. Choi G, Lee S, Lee H, Ko S, Chae C, Han H. Membrane-Associated Effects of Glucocorticoid on BACE1 Upregulation and A? Generation: Involvement of Lipid Raft-Mediated CREB Activation. J Neurosci. 2017;37:8459-8476 pubmed publisher
    ..In this study, we revealed the importance of nongenomic pathway induced by glucocorticoid where membrane glucocorticoid receptor plays an important role in A? formation. ..
  23. Moriishi K. The potential of signal peptide peptidase as a therapeutic target for hepatitis C. Expert Opin Ther Targets. 2017;21:827-836 pubmed publisher
    ..DAA-resistant viruses have also been reported. Development of SPP-selective inhibitors may improve current HCV therapies by decreasing in the emergence of DAA-resistant viruses irrespective of viral genotype. ..
  24. Marambaud P, Ancolio K, Alves Da Costa C, Checler F. Effect of protein kinase A inhibitors on the production of Abeta40 and Abeta42 by human cells expressing normal and Alzheimer's disease-linked mutated betaAPP and presenilin 1. Br J Pharmacol. 1999;126:1186-90 pubmed
    ..Selective inhibitors of protein kinase A may be of therapeutic value in both sporadic and Familial Alzheimer's disease, since they may decrease the production of Abeta that is thought to be responsible for the neurodegenerative process. ..
  25. Huang M, Jiang X, Liang Y, Liu Q, Chen S, Guo Y. Berberine improves cognitive impairment by promoting autophagic clearance and inhibiting production of ?-amyloid in APP/tau/PS1 mouse model of Alzheimer's disease. Exp Gerontol. 2017;91:25-33 pubmed publisher
    ..In summary, berberine shows neuroprotective effects on 3×Tg-AD mice and may be a promising multitarget drug in the preventionand protection against AD. ..
  26. Jing L, Guo D, Hu W, Niu X. The prediction of a pathogenesis-related secretome of Puccinia helianthi through high-throughput transcriptome analysis. BMC Bioinformatics. 2017;18:166 pubmed publisher
  27. Rahimi Aliabadi S, Shahmohammadibeni N, Jamshidi J, Shandiz E, Mirfakhraie R, Ohadi M, et al. Association of ?-Secretase Functional Polymorphism with Risk of Schizophrenia. Genet Test Mol Biomarkers. 2017;21:248-251 pubmed publisher
    ..Our data indicate that rs490460 is associated with the risk of SZ. In silico analysis indicates that rs490460 may be a potential splicing site, which affects protein structure. Replication studies are needed to confirm our data. ..
  28. Gowrishankar S, Wu Y, Ferguson S. Impaired JIP3-dependent axonal lysosome transport promotes amyloid plaque pathology. J Cell Biol. 2017;216:3291-3305 pubmed publisher
  29. Fahlbusch B, Heinrich J, Gross I, Jager L, Richter K, Wichmann H. Allergens in house-dust samples in Germany: results of an East-West German comparison. Allergy. 1999;54:1215-22 pubmed
  30. Qi Y, Klyubin I, Harney S, Hu N, Cullen W, Grant M, et al. Longitudinal testing of hippocampal plasticity reveals the onset and maintenance of endogenous human Aß-induced synaptic dysfunction in individual freely behaving pre-plaque transgenic rats: rapid reversal by anti-Aß agents. Acta Neuropathol Commun. 2014;2:175 pubmed publisher
  31. Cai D, Wang H, He P, Zhu C, Wang Q, Wei X, et al. A novel strategy to improve protein secretion via overexpression of the SppA signal peptide peptidase in Bacillus licheniformis. Microb Cell Fact. 2017;16:70 pubmed publisher
    ..licheniformis. Our results indicate that the sppA overexpression strain, B. licheniformis BL10GS, could be used as a promising host strain for the industrial production of heterologous secreted proteins. ..
  32. Jules F, Sauvageau E, Dumaresq Doiron K, Mazzaferri J, Haug Kröper M, Fluhrer R, et al. CLN5 is cleaved by members of the SPP/SPPL family to produce a mature soluble protein. Exp Cell Res. 2017;357:40-50 pubmed publisher
    ..The remaining N-terminal fragment is then cleaved by SPPL3 and SPPL2b and degraded in the proteasome. This work further characterizes the biology of CLN5 in the hopes of identifying a novel therapeutic strategy for affected children. ..
  33. Lich J, Elliott J, Blum J. Cytoplasmic processing is a prerequisite for presentation of an endogenous antigen by major histocompatibility complex class II proteins. J Exp Med. 2000;191:1513-24 pubmed
    ..Furthermore, two cytoplasmic proteases, the proteasome and calpain, appear to play important roles in MHC class II-restricted antigen presentation. ..
  34. Lo A, Haass C, Wagner S, Teplow D, Sisodia S. Metabolism of the "Swedish" amyloid precursor protein variant in Madin-Darby canine kidney cells. J Biol Chem. 1994;269:30966-73 pubmed
    ..Finally, we demonstrate that A beta is secreted into the basolateral compartment of SWE cells and that the majority of these A beta-related species contains an amino-terminal aspartate residue (+1). ..
  35. Vullhorst D, Ahmad T, Karavanova I, Keating C, Buonanno A. Structural Similarities between Neuregulin 1-3 Isoforms Determine Their Subcellular Distribution and Signaling Mode in Central Neurons. J Neurosci. 2017;37:5232-5249 pubmed publisher
  36. Moussa C. Beta-secretase inhibitors in phase I and phase II clinical trials for Alzheimer's disease. Expert Opin Investig Drugs. 2017;26:1131-1136 pubmed publisher
    ..We may have to seriously consider shifting attention to therapeutic strategies other than BACE1 inhibition or reduction of A? alone and pay more attention to simultaneous clearance of tau and A?. ..
  37. Ostalecki C, Lee J, Dindorf J, Collenburg L, Schierer S, Simon B, et al. Multiepitope tissue analysis reveals SPPL3-mediated ADAM10 activation as a key step in the transformation of melanocytes. Sci Signal. 2017;10: pubmed publisher
    ..Our findings suggest that systematic tissue antigen analysis could complement whole-genome approaches to provide more insight into cancer development. ..
  38. Qin X, Wang Y, Paudel H. Inhibition of Early Growth Response 1 in the Hippocampus Alleviates Neuropathology and Improves Cognition in an Alzheimer Model with Plaques and Tangles. Am J Pathol. 2017;187:1828-1847 pubmed publisher
    ..Egr-1 regulates tau phosphorylation and A? synthesis in the brain by respectively controlling activities of Cdk5 and BACE-1, suggesting that Egr-1 is a potential therapeutic candidate for the treatment of AD. ..
  39. Mamada N, Tanokashira D, Ishii K, Tamaoka A, Araki W. Mitochondria are devoid of amyloid ?-protein (A?)-producing secretases: Evidence for unlikely occurrence within mitochondria of A? generation from amyloid precursor protein. Biochem Biophys Res Commun. 2017;486:321-328 pubmed publisher
    ..In view of the particularly low expression levels of BACE1, ?-secretase complex proteins, and ?-CTF in mitochondria, we propose that it is unlikely that A? generation from APP occurs locally within this organelle. ..
  40. Rekhtman N, Kazi S. Nonspecific reactivity of polyclonal napsin a antibody in mucinous adenocarcinomas of various sites: a word of caution. Arch Pathol Lab Med. 2015;139:434-6 pubmed publisher
  41. Ehlert F, Linde K, Diederich W. What Are We Missing? The Detergent Triton X-100 Added to Avoid Compound Aggregation Can Affect Assay Results in an Unpredictable Manner. ChemMedChem. 2017;12:1419-1423 pubmed publisher
  42. Piljić Burazer M, Mladinov S, Capkun V, Kuret S, Glavina Durdov M. The Utility of Thyroid Transcription Factor 1 (TTF-1), Napsin A, Excision Repair Cross-Complementing 1 (ERCC1), Anaplastic Lymphoma Kinase (ALK) and the Epidermal Growth Factor Receptor (EGFR) Expression in Small Biopsy in Prognosis of Patients with . Med Sci Monit. 2017;23:489-497 pubmed
    ..The percentages of EGFR and ALK mutations corresponded to those in previously published reports for Caucasians. ..
  43. Zhang S, Wang Z, Cai F, Zhang M, Wu Y, Zhang J, et al. BACE1 Cleavage Site Selection Critical for Amyloidogenesis and Alzheimer's Pathogenesis. J Neurosci. 2017;37:6915-6925 pubmed publisher
  44. Ye X, Feng T, Tammineni P, Chang Q, Jeong Y, Margolis D, et al. Regulation of Synaptic Amyloid-? Generation through BACE1 Retrograde Transport in a Mouse Model of Alzheimer's Disease. J Neurosci. 2017;37:2639-2655 pubmed publisher
    ..Our study uncovers a new pathway that controls synaptic APP processing by enhancing axonal BACE1 trafficking, thereby advancing our fundamental knowledge critical for ameliorating A?-linked synaptic pathology. ..
  45. Rakoczy P, Lai C, Baines M, Di Grandi S, Fitton J, Constable I. Modulation of cathepsin D activity in retinal pigment epithelial cells. Biochem J. 1997;324 ( Pt 3):935-40 pubmed
    ..These results demonstrate that cathepsin D is a major proteolytic enzyme participating in the lysosomal digestion of photoreceptor outer segments. ..
  46. Furukawa K, Sopher B, Rydel R, Begley J, Pham D, Martin G, et al. Increased activity-regulating and neuroprotective efficacy of alpha-secretase-derived secreted amyloid precursor protein conferred by a C-terminal heparin-binding domain. J Neurochem. 1996;67:1882-96 pubmed
  47. Rossi G, Cadioli A, Mengoli M, Piccioli S, Cavazza A. Napsin A expression in pulmonary sclerosing haemangioma. Histopathology. 2012;60:361-3 pubmed publisher
  48. Nigam S, Xu S, Kritikou J, Marosi K, Brodin L, Mattson M. Exercise and BDNF reduce A? production by enhancing ?-secretase processing of APP. J Neurochem. 2017;142:286-296 pubmed publisher
    ..Exercise and other factors that enhance BDNF signaling may therefore have both therapeutic and prophylactic value in the battle against AD. Read the Editorial Highlight for this article on page 191. ..
  49. Mizuguchi K, Deane C, Blundell T, Overington J. HOMSTRAD: a database of protein structure alignments for homologous families. Protein Sci. 1998;7:2469-71 pubmed
    ..The database is freely available on the World Wide Web at: http://www-cryst.bioc.cam. ac.uk/-homstrad/, with search facilities and links to other databases. ..