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Top Publications

  1. Suzuki S, Solberg L, Redei E, Handa R. Prepro-thyrotropin releasing hormone 178-199 immunoreactivity is altered in the hypothalamus of the Wistar-Kyoto strain of rat. Brain Res. 2001;913:224-33 pubmed
    ..Such data fit with the hypothesis that PPTRH 178-199 is involved in the regulation of the HPA axis and behavior. ..
  2. Sedmera D, Harris B, Grant E, Zhang N, Jourdan J, Kurkova D, et al. Cardiac expression patterns of endothelin-converting enzyme (ECE): implications for conduction system development. Dev Dyn. 2008;237:1746-53 pubmed publisher
    ..In vivo, ET receptor blockade with bosentan delayed activation sequence maturation. These data support a role for ECE in avian cardiac conduction system differentiation and maturation. ..
  3. Tian G, Ghanekar S, Aharony D, Shenvi A, Jacobs R, Liu X, et al. The mechanism of gamma-secretase: multiple inhibitor binding sites for transition state analogs and small molecule inhibitors. J Biol Chem. 2003;278:28968-75 pubmed
    ..These findings provide useful insights into the catalytic and regulatory mechanisms of gamma-secretase that may facilitate the design of novel gamma-secretase inhibitors. ..
  4. Michaelis M. Drugs targeting Alzheimer's disease: some things old and some things new. J Pharmacol Exp Ther. 2003;304:897-904 pubmed
    ..Nevertheless, the pace of recent research clearly supports optimism that slowing progression of AD will soon be possible. ..
  5. Zhang Z, ElSohly H, Jacob M, Pasco D, Walker L, Clark A. New sesquiterpenoids from the root of Guatteria multivenia. J Nat Prod. 2002;65:856-9 pubmed
    ..albicans, Cryptococcusneoformans, Staphylococcus aureus, and methicillin-resistant S. aureus (MRS) with IC(50)/MIC values of 3.5/6.25, 2.0/12.5, 2.0/3.13, and 2.0/3.13 microg/mL, respectively. ..
  6. Schofield D, Westwater C, Warner T, Nicholas P, Paulling E, Balish E. Hydrolytic gene expression during oroesophageal and gastric candidiasis in immunocompetent and immunodeficient gnotobiotic mice. J Infect Dis. 2003;188:591-9 pubmed
  7. Ganesh O, Green T, Edison A, Hagen S. Characterizing the residue level folding of the intrinsically unstructured IA3. Biochemistry. 2006;45:13585-96 pubmed
    ..When combined with a traditional biochemical understanding of interactions between individual residues, this approach leads to a better understanding of protein folding. ..
  8. Golde T, Wolfe M, Greenbaum D. Signal peptide peptidases: a family of intramembrane-cleaving proteases that cleave type 2 transmembrane proteins. Semin Cell Dev Biol. 2009;20:225-30 pubmed publisher
    ..Further study of the SPP family is needed in order to understand their biological roles and their potential as therapeutic targets. ..
  9. Muresan Z, Muresan V. Neuritic deposits of amyloid-beta peptide in a subpopulation of central nervous system-derived neuronal cells. Mol Cell Biol. 2006;26:4982-97 pubmed
    ..CAD cells appear to recapitulate the biochemical processes leading to Abeta deposition, thus providing an experimental in vitro system for studying the molecular pathobiology of AD. ..

More Information


  1. Marcinkeviciene J, Kopcho L, Yang T, Copeland R, Glass B, Combs A, et al. Novel inhibition of porcine pepsin by a substituted piperidine. Preference for one of the enzyme conformers. J Biol Chem. 2002;277:28677-82 pubmed
    ..Taken together, these data suggest that the enzyme can readily interconvert between two conformers, one capable of binding substrate and pepstatin A and the other capable of binding the substituted piperidine. ..
  2. Li T, Yowell C, Beyer B, Hung S, Westling J, Lam M, et al. Recombinant expression and enzymatic subsite characterization of plasmepsin 4 from the four Plasmodium species infecting man. Mol Biochem Parasitol. 2004;135:101-9 pubmed
    ..falciparum having Ser in P3' had the lowest Ki of the series of inhibitors prepared, but did not significantly improve the selectivity of the inhibitor for plasmepsin 4 versus human cathepsin D. ..
  3. Woodard Grice A, McBrayer A, Wakefield J, Zhuo Y, Bellis S. Proteolytic shedding of ST6Gal-I by BACE1 regulates the glycosylation and function of alpha4beta1 integrins. J Biol Chem. 2008;283:26364-73 pubmed publisher
    ..Collectively, these results describe a novel mechanism for alpha4beta1 regulation and further suggest an unanticipated role for BACE1 in macrophage function. ..
  4. Tian G, Sobotka Briner C, Zysk J, Liu X, Birr C, Sylvester M, et al. Linear non-competitive inhibition of solubilized human gamma-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines. J Biol Chem. 2002;277:31499-505 pubmed
    ..Models to rationalize how transition state analogs inhibit their targets by non-competitive inhibition are discussed. ..
  5. Beyer B, Johnson J, Chung A, Li T, Madabushi A, Agbandje McKenna M, et al. Active-site specificity of digestive aspartic peptidases from the four species of Plasmodium that infect humans using chromogenic combinatorial peptide libraries. Biochemistry. 2005;44:1768-79 pubmed
    ..Some of these compounds were potent inhibitors of the five plasmepsins, and their possible binding modes were analyzed by computational methods. ..
  6. Ko M, Puglielli L. Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based lysine acetyltransferases post-translationally regulate BACE1 levels. J Biol Chem. 2009;284:2482-92 pubmed publisher
    ..The biochemical characterization of the above events could lead to the identification of novel pharmacological strategies for the prevention of this form of dementia. ..
  7. Green J, Xie S, Gan X, Roberts R. An aspartic proteinase expressed in the equine placenta. Adv Exp Med Biol. 1998;436:163-7 pubmed
    ..The high sequence identity that ePAG shares with pepsinogens as well as the PAG, indicates that ePAG may be the evolutionary bridge that links these two groups of aspartic proteinases. ..
  8. Nyborg A, Kornilova A, Jansen K, Ladd T, Wolfe M, Golde T. Signal peptide peptidase forms a homodimer that is labeled by an active site-directed gamma-secretase inhibitor. J Biol Chem. 2004;279:15153-60 pubmed
    ..Collectively these data suggest that SPP exists in vivo as a functional dimer. ..
  9. Jonas M, Costantini C, Puglielli L. PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1. EMBO Rep. 2008;9:916-22 pubmed publisher
    ..In addition, Pcsk9(-/-) mice showed increased levels of BACE1 and Abeta in the brain. Finally, we found that nascent low-density lipoprotein receptor, a known substrate of PCSK9, is also acetylated. ..
  10. Varvel N, Bhaskar K, Patil A, Pimplikar S, Herrup K, Lamb B. Abeta oligomers induce neuronal cell cycle events in Alzheimer's disease. J Neurosci. 2008;28:10786-93 pubmed publisher
    ..Together, our data suggest that low molecular weight aggregates of Abeta induce neuronal cell cycle re-entry in mouse models of Alzheimer's disease. ..
  11. Costantini C, Ko M, Jonas M, Puglielli L. A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1. Biochem J. 2007;407:383-95 pubmed
    ..Site-directed mutagenesis indicates that lysine acetylation is necessary for nascent BACE1 to leave the ER and move ahead in the secretory pathway, and for the molecular stabilization of the protein. ..
  12. Villar C, Kashleva H, Nobile C, Mitchell A, Dongari Bagtzoglou A. Mucosal tissue invasion by Candida albicans is associated with E-cadherin degradation, mediated by transcription factor Rim101p and protease Sap5p. Infect Immun. 2007;75:2126-35 pubmed
    ..Our data support the hypothesis that there is a mechanism by which C. albicans invades mucosal tissues by promoting the proteolytic degradation of E-cadherin in epithelial adherens junctions. ..
  13. Han S, Green L, Schnell D. The signal peptide peptidase is required for pollen function in Arabidopsis. Plant Physiol. 2009;149:1289-301 pubmed publisher
    ..These data demonstrate that AtSPP is required for male gametophyte development and pollen maturation in Arabidopsis. ..
  14. Robbins A, Dunn B, Agbandje McKenna M, McKenna R. Crystallographic evidence for noncoplanar catalytic aspartic acids in plasmepsin II resides in the Protein Data Bank. Acta Crystallogr D Biol Crystallogr. 2009;65:294-6 pubmed publisher
    ..9 A resolution published diffraction data to an R(cryst) of 21.2% and an R(free) of 22.2%. The catalytic water molecule is present, but the plane of the carboxylate group of Asp214 is rotated by 66 degrees from its original position. ..
  15. Klionsky D, Emr S. Membrane protein sorting: biosynthesis, transport and processing of yeast vacuolar alkaline phosphatase. EMBO J. 1989;8:2241-50 pubmed
    ..These results indicate that ALP will be a useful model protein for studies of membrane protein sorting in yeast. ..
  16. Murphy M, Golde T. Inclusion-body myositis and Alzheimer disease: two sides of the same coin, or different currencies altogether?. Neurology. 2006;66:S65-8 pubmed
  17. Yue X, Lu M, Lancaster T, Cao P, Honda S, Staufenbiel M, et al. Brain estrogen deficiency accelerates Abeta plaque formation in an Alzheimer's disease animal model. Proc Natl Acad Sci U S A. 2005;102:19198-203 pubmed
    ..Our results indicate that estrogen depletion in the brain may be a significant risk factor for developing AD neuropathology. ..
  18. Kukar T, Murphy M, Eriksen J, Sagi S, Weggen S, Smith T, et al. Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production. Nat Med. 2005;11:545-50 pubmed
  19. Camden J, Schrader A, Camden R, Gonzalez F, Erb L, Seye C, et al. P2Y2 nucleotide receptors enhance alpha-secretase-dependent amyloid precursor protein processing. J Biol Chem. 2005;280:18696-702 pubmed
    ..These results may contribute to an understanding of the non-amyloidogenic processing of APP. ..
  20. Vadaie N, Dionne H, Akajagbor D, Nickerson S, Krysan D, Cullen P. Cleavage of the signaling mucin Msb2 by the aspartyl protease Yps1 is required for MAPK activation in yeast. J Cell Biol. 2008;181:1073-81 pubmed publisher
    ..We postulate that cleavage-dependent activation is a general feature of signaling mucins, which brings to light a novel regulatory aspect of this class of signaling adhesion molecule. ..
  21. Knappenberger K, Tian G, Ye X, Sobotka Briner C, Ghanekar S, Greenberg B, et al. Mechanism of gamma-secretase cleavage activation: is gamma-secretase regulated through autoinhibition involving the presenilin-1 exon 9 loop?. Biochemistry. 2004;43:6208-18 pubmed
    ..It is possible that the DeltaE9 mutation causes Alzheimer's disease because cleavage activation of gamma-secretase is no longer necessary, alleviating constraints on Abeta formation. ..
  22. Ergul A, Grubbs A, Zhang Y, Spinale F. Selective upregulation of endothelin converting enzyme-1a in the human failing heart. J Card Fail. 2000;6:314-20 pubmed
    ..This study showed that the biosynthetic pathway of ET-1 is activated in LV myocardium in the failing heart, and the myocardial processing of big ET-1 is highly specific for ECE-1. ..
  23. Xie S, Green J, Bixby J, Szafranska B, DeMartini J, Hecht S, et al. The diversity and evolutionary relationships of the pregnancy-associated glycoproteins, an aspartic proteinase subfamily consisting of many trophoblast-expressed genes. Proc Natl Acad Sci U S A. 1997;94:12809-16 pubmed
  24. Searfoss G, Jordan W, Calligaro D, Galbreath E, Schirtzinger L, Berridge B, et al. Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor. J Biol Chem. 2003;278:46107-16 pubmed
    ..Additionally, the aberrant expression of adipsin, and its presence in feces may serve as a noninvasive biomarker of gastrointestinal toxicity associated with perturbed Notch signaling. ..
  25. He P, Zhong Z, Lindholm K, Berning L, Lee W, Lemere C, et al. Deletion of tumor necrosis factor death receptor inhibits amyloid beta generation and prevents learning and memory deficits in Alzheimer's mice. J Cell Biol. 2007;178:829-41 pubmed
    ..These findings suggest that TNFR1 not only contributes to neurodegeneration but also that it is involved in APP processing and Abeta plaque formation. Thus, TNFR1 is a novel therapeutic target for AD. ..
  26. He W, Shi Q, Hu X, Yan R. The membrane topology of RTN3 and its effect on binding of RTN3 to BACE1. J Biol Chem. 2007;282:29144-51 pubmed
    ..Thus, the determination of RTN3 membrane topology may provide an important structural basis for our understanding of its cellular functions. ..
  27. Zhang Z, ElSohly H, Jacob M, Pasco D, Walker L, Clark A. Natural products inhibiting Candida albicans secreted aspartic proteases from Lycopodium cernuum. J Nat Prod. 2002;65:979-85 pubmed
    ..Compounds 1 and 11 showed inhibitory effects against C. albicans secreted aspartic proteases (SAP) with IC50 of 20 and 8.5 microg/mL, respectively, while the other compounds were inactive...
  28. Marlow L, Canet R, Haugabook S, Hardy J, Lahiri D, Sambamurti K. APH1, PEN2, and Nicastrin increase Abeta levels and gamma-secretase activity. Biochem Biophys Res Commun. 2003;305:502-9 pubmed
    ..In addition, our studies also suggest that the presenilin partners regulate the relative levels of Abeta40 and Abeta42. ..
  29. Green J, Xie S, Quan X, Bao B, Gan X, Mathialagan N, et al. Pregnancy-associated bovine and ovine glycoproteins exhibit spatially and temporally distinct expression patterns during pregnancy. Biol Reprod. 2000;62:1624-31 pubmed
    ..It seems likely that some of the newly discovered PAG will be better candidates than PAG-1 for pregnancy diagnosis. ..
  30. Ikezu T, Trapp B, Song K, Schlegel A, Lisanti M, Okamoto T. Caveolae, plasma membrane microdomains for alpha-secretase-mediated processing of the amyloid precursor protein. J Biol Chem. 1998;273:10485-95 pubmed
    ..Conversely, caveolin depletion using antisense oligonucletotides prevented this cleavage event. Our current results indicate that caveolae and caveolins may play a pivotal role in the alpha-secretase-mediated proteolysis of APP in vivo. ..
  31. Kanning K, Hudson M, Amieux P, Wiley J, Bothwell M, Schecterson L. Proteolytic processing of the p75 neurotrophin receptor and two homologs generates C-terminal fragments with signaling capability. J Neurosci. 2003;23:5425-36 pubmed
  32. Ishimura N, Bronk S, Gores G. Inducible nitric oxide synthase up-regulates Notch-1 in mouse cholangiocytes: implications for carcinogenesis. Gastroenterology. 2005;128:1354-68 pubmed
    ..These data implicate a direct link between the inflammatory mediator iNOS and Notch signaling, and have implications for the development and progression of cholangiocarcinoma. ..
  33. Yang Y, Kinney G, Spain W, Breitner J, Cook D. Presenilin-1 and intracellular calcium stores regulate neuronal glutamate uptake. J Neurochem. 2004;88:1361-72 pubmed
    ..Taken together, these findings indicate that PS1 and intracellular calcium stores may play a significant role in regulating glutamate uptake and therefore may be important in limiting glutamate toxicity in the brain. ..
  34. Saless N, Litscher S, Lopez Franco G, Houlihan M, Sudhakaran S, Raheem K, et al. Quantitative trait loci for biomechanical performance and femoral geometry in an intercross of recombinant congenic mice: restriction of the Bmd7 candidate interval. FASEB J. 2009;23:2142-54 pubmed publisher
  35. Chiocco M, Kulnane L, Younkin L, Younkin S, Evin G, Lamb B. Altered amyloid-beta metabolism and deposition in genomic-based beta-secretase transgenic mice. J Biol Chem. 2004;279:52535-42 pubmed
    ..Our studies demonstrate, for the first time, that modulation of BACE1 activity may play a significant role in AD pathogenesis in vivo. ..
  36. McPhie D, Golde T, Eckman C, Yager D, Brant J, Neve R. beta-Secretase cleavage of the amyloid precursor protein mediates neuronal apoptosis caused by familial Alzheimer's disease mutations. Brain Res Mol Brain Res. 2001;97:103-13 pubmed
    ..It may be inferred from these data that beta-secretase cleavage of FAD mutants of APP allows the appropriate caspase access to its site of action to produce C31, which directly causes neuronal apoptosis. ..
  37. Xie S, Low B, Nagel R, Kramer K, Anthony R, Zoli A, et al. Identification of the major pregnancy-specific antigens of cattle and sheep as inactive members of the aspartic proteinase family. Proc Natl Acad Sci U S A. 1991;88:10247-51 pubmed
    ..Critical amino acid substitutions at the active site regions suggest that both proteins are enzymatically inactive. The antigen is a product of trophoblast binucleate cells that invade maternal endometrium at implantation sites. ..
  38. Tomita T. Immunocytochemical localization of prohormone convertase 1/3 and 2 in pancreatic islet cells and islet cell tumors. Pancreas. 2001;23:172-6 pubmed
  39. He W, Lu Y, Qahwash I, Hu X, Chang A, Yan R. Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation. Nat Med. 2004;10:959-65 pubmed
    ..Thus, changes in the expression of reticulon proteins in the human brain are likely to affect cellular amyloid-beta and the formation of amyloid plaques. ..
  40. Thirumangalakudi L, Prakasam A, Zhang R, Bimonte Nelson H, Sambamurti K, Kindy M, et al. High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in mice. J Neurochem. 2008;106:475-85 pubmed publisher
    ..The findings link hypercholesterolemia with cognitive dysfunction potentially mediated by increased neuroinflammation and APP processing in a non-transgenic mouse model. ..
  41. Wang W, Rajeev B, Stromberg A, Ren N, Tang G, Huang Q, et al. The expression of microRNA miR-107 decreases early in Alzheimer's disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1. J Neurosci. 2008;28:1213-23 pubmed publisher
  42. Hyndman K, Evans D. Endothelin and endothelin converting enzyme-1 in the fish gill: evolutionary and physiological perspectives. J Exp Biol. 2007;210:4286-97 pubmed
    ..From our phylogenetic analyses, ECE is predicted to have an ancient origin and may be a generalist endoprotease in non-vertebrate organisms, while EDNs are vertebrate-specific peptides and may be key characters in vertebrate evolution. ..
  43. Murphy M, Das P, Nyborg A, Rochette M, Dodson M, Loosbrock N, et al. Overexpression of nicastrin increases Abeta production. FASEB J. 2003;17:1138-40 pubmed
  44. Eckman E, Adams S, Troendle F, Stodola B, Kahn M, Fauq A, et al. Regulation of steady-state beta-amyloid levels in the brain by neprilysin and endothelin-converting enzyme but not angiotensin-converting enzyme. J Biol Chem. 2006;281:30471-8 pubmed
  45. Nyborg A, Ladd T, Jansen K, Kukar T, Golde T. Intramembrane proteolytic cleavage by human signal peptide peptidase like 3 and malaria signal peptide peptidase. FASEB J. 2006;20:1671-9 pubmed
    ..Based on these data, we hypothesize that mSPP is a potential a novel therapeutic target for malaria. ..
  46. Li R, Lindholm K, Yang L, Yue X, Citron M, Yan R, et al. Amyloid beta peptide load is correlated with increased beta-secretase activity in sporadic Alzheimer's disease patients. Proc Natl Acad Sci U S A. 2004;101:3632-7 pubmed
  47. Sambamurti K, Kinsey R, Maloney B, Ge Y, Lahiri D. Gene structure and organization of the human beta-secretase (BACE) promoter. FASEB J. 2004;18:1034-6 pubmed
    ..Such a study will allow us to further examine the possible role of changes in the promoter of BACE in AD pathogenesis. ..
  48. Stein T, Anders N, DeCarli C, Chan S, Mattson M, Johnson J. Neutralization of transthyretin reverses the neuroprotective effects of secreted amyloid precursor protein (APP) in APPSW mice resulting in tau phosphorylation and loss of hippocampal neurons: support for the amyloid hypothesis. J Neurosci. 2004;24:7707-17 pubmed
    ..Therefore, the elevated expression of transthyretin is mediated by sAPPalpha and protects APP(Sw) mice from developing many of the neuropathologies observed in AD. ..
  49. Chen X, Rosenfeld C, Roberts R, Green J. An aspartic proteinase expressed in the yolk sac and neonatal stomach of the mouse. Biol Reprod. 2001;65:1092-101 pubmed
    ..The presence of this enzyme in two organs involved in the selective transcellular transport of proteins suggests that it has specialized digestive functions. ..
  50. Szafranska B, Miura R, Ghosh D, Ezashi T, Xie S, Roberts R, et al. Gene for porcine pregnancy-associated glycoprotein 2 (poPAG2): its structural organization and analysis of its promoter. Mol Reprod Dev. 2001;60:137-46 pubmed
    ..In the non-trophoblast cell lines, Ets2 failed to elicit any response. Ets2 responsiveness may be a common feature of most or all trophoblast-expressed genes, although in the case of poPAG2, the effect may be indirect. ..
  51. Sen U, Tyagi N, Patibandla P, Dean W, Tyagi S, Roberts A, et al. Fibrinogen-induced endothelin-1 production from endothelial cells. Am J Physiol Cell Physiol. 2009;296:C840-7 pubmed publisher
    ..Thus, an increased content of Fg may enhance vasoconstriction through increased production of ET-1. ..