NEU3

Summary

Gene Symbol: NEU3
Description: sialidase 3 (membrane sialidase)
Alias: SIAL3, N-acetyl-alpha-neuraminidase 3, ganglioside sialidase, membrane sialidase, neuraminidase 3, sialidase-3
Species: human

Top Publications

  1. doi New findings on nuclear gangliosides: overview on metabolism and function
    Robert Ledeen
    Department of Neurology and Neurosciences, New Jersey Medical School, UMDNJ, Newark, NJ 07103, USA
    J Neurochem 116:714-20. 2011
  2. ncbi High mannose glycans and sialic acid on gp120 regulate binding of mannose-binding lectin (MBL) to HIV type 1
    Melanie L Hart
    Rush Presbyterian St Luke s Medical Center, Department of Immunology Microbiology, Chicago, Illinois 60612, USA
    AIDS Res Hum Retroviruses 18:1311-7. 2002
  3. pmc Gangliosides play an important role in the organization of CD82-enriched microdomains
    Elena Odintsova
    Cancer Research U K Institute for Cancer Studies, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
    Biochem J 400:315-25. 2006
  4. ncbi Molecular cloning and characterization of a plasma membrane-associated sialidase specific for gangliosides
    T Miyagi
    Division of Biochemistry, Research Institute, Miyagi Prefectural Cancer Center, Natori, Miyagi, 981 1293, Japan
    J Biol Chem 274:5004-11. 1999
  5. doi Regulation of plasma-membrane-associated sialidase NEU3 gene by Sp1/Sp3 transcription factors
    Kazunori Yamaguchi
    Miyagi Cancer Center Research Institute, Natori, Japan
    Biochem J 430:107-17. 2010
  6. ncbi Dependence of neurotrophic factor activation of Trk tyrosine kinase receptors on cellular sialidase
    Alicja Woronowicz
    Department of Microbiology and Immunology, Queen s University, Kingston, Ontario, Canada
    Glycobiology 17:10-24. 2007
  7. doi Inhibition of human neuraminidase 3 (NEU3) by C9-triazole derivatives of 2,3-didehydro-N-acetyl-neuraminic acid
    Yao Zou
    Alberta Ingenuity Centre for Carbohydrate Science, Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada
    Bioorg Med Chem Lett 20:7529-33. 2010
  8. ncbi Molecular cloning of mouse ganglioside sialidase and its increased expression in Neuro2a cell differentiation
    T Hasegawa
    Division of Biochemistry, Research Institute, Miyagi Prefectural Cancer Center, 47 1 Nodayama, Medeshima shiode, Natori, Miyagi 981 1293, Japan
    J Biol Chem 275:8007-15. 2000
  9. ncbi Plasma membrane production of ceramide from ganglioside GM3 in human fibroblasts
    Rea Valaperta
    Department of Medical Chemistry, Biochemistry and Biotechnology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Fratelli Cervi 93, Segrate 20090, Milan, Italy
    FASEB J 20:1227-9. 2006
  10. doi Identification of lysosomal sialidase NEU1 and plasma membrane sialidase NEU3 in human erythrocytes
    Francesca D'Avila
    Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, F lli Cervi 93, Segrate, Milan 20090, Italy
    J Cell Biochem 114:204-11. 2013

Scientific Experts

  • J Kopitz
  • May M Luke
  • Taeko Miyagi
  • Nicholas M Stamatos
  • Min Zhang
  • Zhiyun Wang
  • Trisha M Finlay
  • Elena Odintsova
  • Sadagopan Magesh
  • Shigeki Katoh
  • M Hiraiwa
  • Gusheng Wu
  • Yutaro Azuma
  • E Monti
  • Robert Ledeen
  • Ming Luo
  • Alan Cross
  • Kazunori Yamaguchi
  • Bruno Venerando
  • Luigi Anastasia
  • Cristina Tringali
  • Kazuhiro Shiozaki
  • Nadia Papini
  • Guido Tettamanti
  • Massimo Aureli
  • Tadashi Wada
  • Amgad Albohy
  • Robert W Ledeen
  • Senitiroh Hakomori
  • MIERCIO PEREIRA
  • Sandro Sonnino
  • Alessandro Prinetti
  • Vanna Chigorno
  • Keiko Hata
  • Roberto Bresciani
  • Edoardo Giacopuzzi
  • T Wada
  • Christopher W Cairo
  • Koichi Koseki
  • Setsuko Moriya
  • Giuseppe Borsani
  • Augusto Preti
  • Cheorl Ho Kim
  • Rea Valaperta
  • Francesca D'Avila
  • Nicoletta Loberto
  • Ikuro Sato
  • Jeong Heon Ko
  • Marta Manzoni
  • K Yamaguchi
  • Ki Tae Ha
  • Hideaki Yamanami
  • S Kawamura
  • Volkan Seyrantepe
  • Alan S Cross
  • Fang Ma
  • Roland Schauer
  • Mahendra S Sandbhor
  • Maiko Miyata
  • Dirk Wipfler
  • Yoichiro Kakugawa
  • Ruixiang Blake Zheng
  • Maurilio Sampaolesi
  • Yao Zou
  • Loredana Dileo
  • Chandan Mandal
  • Hisashi Narimatsu
  • Momo Shiozaki
  • S Moriya
  • Ivan Carubelli
  • Jianfeng Wang
  • C Tringali
  • Un Ho Jin
  • Sung Koo Kang
  • Samah Zeineb Gadhoum
  • Young Chae Chang
  • Minyoung Lee
  • Anna Bianchi
  • Hiroo Tateno
  • Kyung Woon Kim
  • Xinli Nan
  • Alicja Woronowicz
  • Shinsuke Yoshizumi
  • Gabriele Zanchetti
  • Sung Kwon Moon
  • Paolo Colombi
  • Young Choon Lee
  • Kengo Kato
  • Seiji Ueno
  • Feng Liang

Detail Information

Publications85

  1. doi New findings on nuclear gangliosides: overview on metabolism and function
    Robert Ledeen
    Department of Neurology and Neurosciences, New Jersey Medical School, UMDNJ, Newark, NJ 07103, USA
    J Neurochem 116:714-20. 2011
    ..The Neu3 isoform of neuraminidase occurs in the inner membrane of the NE and Neu1 in the outer membrane...
  2. ncbi High mannose glycans and sialic acid on gp120 regulate binding of mannose-binding lectin (MBL) to HIV type 1
    Melanie L Hart
    Rush Presbyterian St Luke s Medical Center, Department of Immunology Microbiology, Chicago, Illinois 60612, USA
    AIDS Res Hum Retroviruses 18:1311-7. 2002
    ..These studies provide evidence that MBL binds to HIV via high mannose carbohydrates on gp120 and shows that the interaction of MBL with virus is regulated by sialylation...
  3. pmc Gangliosides play an important role in the organization of CD82-enriched microdomains
    Elena Odintsova
    Cancer Research U K Institute for Cancer Studies, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
    Biochem J 400:315-25. 2006
    ..Furthermore, ectopic expression of the plasma-membrane-bound sialidase Neu3 in mammary epithelial cells also affected stability of the complexes containing CD82: its association with ..
  4. ncbi Molecular cloning and characterization of a plasma membrane-associated sialidase specific for gangliosides
    T Miyagi
    Division of Biochemistry, Research Institute, Miyagi Prefectural Cancer Center, Natori, Miyagi, 981 1293, Japan
    J Biol Chem 274:5004-11. 1999
    ..Here we describe the cloning and expression of a cDNA for the ganglioside sialidase, isolated from a bovine brain cDNA library based on the amino acid sequence of the purified enzyme from ..
  5. doi Regulation of plasma-membrane-associated sialidase NEU3 gene by Sp1/Sp3 transcription factors
    Kazunori Yamaguchi
    Miyagi Cancer Center Research Institute, Natori, Japan
    Biochem J 430:107-17. 2010
    Gene expression of the human plasma membrane-associated sialidase (NEU3), a key enzyme for ganglioside degradation, is relatively high in brain and is modulated in response to many cellular processes, including neuronal cell ..
  6. ncbi Dependence of neurotrophic factor activation of Trk tyrosine kinase receptors on cellular sialidase
    Alicja Woronowicz
    Department of Microbiology and Immunology, Queen s University, Kingston, Ontario, Canada
    Glycobiology 17:10-24. 2007
    ..Here, we discover a membrane sialidase-controlling mechanism that depends on ligand binding to its receptor to induce enzyme activity which targets ..
  7. doi Inhibition of human neuraminidase 3 (NEU3) by C9-triazole derivatives of 2,3-didehydro-N-acetyl-neuraminic acid
    Yao Zou
    Alberta Ingenuity Centre for Carbohydrate Science, Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada
    Bioorg Med Chem Lett 20:7529-33. 2010
    ..modified analogs of 2,3-didehydro-N-acetyl-neuraminic acid (DANA) and their inhibitory potency for the human neuraminidase 3 (NEU3) enzyme...
  8. ncbi Molecular cloning of mouse ganglioside sialidase and its increased expression in Neuro2a cell differentiation
    T Hasegawa
    Division of Biochemistry, Research Institute, Miyagi Prefectural Cancer Center, 47 1 Nodayama, Medeshima shiode, Natori, Miyagi 981 1293, Japan
    J Biol Chem 275:8007-15. 2000
    ..further the roles and regulation mechanisms of the sialidase in neuronal systems, we have cloned mouse ganglioside sialidase cDNA and observed its expression in Neuro2a cell differentiation...
  9. ncbi Plasma membrane production of ceramide from ganglioside GM3 in human fibroblasts
    Rea Valaperta
    Department of Medical Chemistry, Biochemistry and Biotechnology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Fratelli Cervi 93, Segrate 20090, Milan, Italy
    FASEB J 20:1227-9. 2006
    ..conditions able to block endocytosis or lysosomal activity, and the overexpression of the plasma membrane ganglioside sialidase Neu3 corresponded to a higher production of ceramide in the plasma membrane...
  10. doi Identification of lysosomal sialidase NEU1 and plasma membrane sialidase NEU3 in human erythrocytes
    Francesca D'Avila
    Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, F lli Cervi 93, Segrate, Milan 20090, Italy
    J Cell Biochem 114:204-11. 2013
    ..Our results demonstrate that: (a) Both sialidases NEU1 and NEU3 are present on erythrocyte plasma membrane; (b) NEU1 is kept on the plasma membrane in absence of the protective ..
  11. ncbi Chronic ethanol feeding controls the activities of various sialidases by regulating their relative synthetic rates in the rat liver
    Magnus A Azuine
    The Lipid Research Laboratory 151 T, Veterans Affairs Medical Center, Washington, DC 20422, USA
    Metabolism 54:1056-64. 2005
    ..b>Ganglioside sialidase activities in the hepatic subcellular fractions were also determined...
  12. pmc Sialidases on mammalian sperm mediate deciduous sialylation during capacitation
    Fang Ma
    Glycobiology Research and Training Center and Departments of Cellular, University of California, San Diego, La Jolla, California 92093 0687, USA
    J Biol Chem 287:38073-9. 2012
    ..We report the presence of two sialidases (neuraminidases Neu1 and Neu3) on mammalian sperm. These are themselves shed from sperm during capacitation...
  13. doi Molecular cloning and biochemical characterization of two novel Neu3 sialidases, neu3a and neu3b, from medaka (Oryzias latipes)
    Kazuhiro Shiozaki
    Faculty of Fisheries, Kagoshima University, Kagoshima, Japan
    Biochimie 95:280-9. 2013
    Mammalian Neu3 sialidases are involved in various biological processes, such as cell death and differentiation, through desialylation of gangliosides. The enzymatic profile of Neu3 seems to be highly conserved from birds to mammals...
  14. ncbi Colon cancer: genomics and apoptotic events
    Charleen Rupnarain
    School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Johannesburg 2050, South Africa
    Biol Chem 385:449-64. 2004
    ..PUMA, 15-LOX-1, ceramide, butyrate, tributyrin and PPARgamma, whereas the molecules which promote colon cancer cell survival are p53 mutants, Bcl-2, Neu3 and COX-2. Cancer therapies aimed at controlling colon cancer are reviewed briefly.
  15. pmc The plasma membrane sialidase NEU3 regulates the malignancy of renal carcinoma cells by controlling β1 integrin internalization and recycling
    Cristina Tringali
    Department of Medical Biotechnology, University of Milan, Segrate, 20090 Milan, Italy
    J Biol Chem 287:42835-45. 2012
    The human plasma membrane sialidase NEU3 is a key enzyme in the catabolism of membrane gangliosides, is crucial in the regulation of cell surface processes, and has been demonstrated to be significantly up-regulated in renal cell ..
  16. pmc NEU1 and NEU3 sialidase activity expressed in human lung microvascular endothelia: NEU1 restrains endothelial cell migration, whereas NEU3 does not
    Alan S Cross
    Center for Vaccine Development, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA
    J Biol Chem 287:15966-80. 2012
    ..b>NEU3 was detected both in the cytosol and nucleus...
  17. pmc New insights on the sialidase protein family revealed by a phylogenetic analysis in metazoa
    Edoardo Giacopuzzi
    Department of Biomedical Sciences and Biotechnology, Unit of Biology and Genetics, University of Brescia, Brescia, Italy
    PLoS ONE 7:e44193. 2012
    ..sialidase forms are known in vertebrates: the lysosomal NEU1, the cytosolic NEU2 and the membrane-associated NEU3 and NEU4...
  18. doi Polymorphisms and noncardioembolic stroke in three case-control studies
    May M Luke
    Celera, Alameda, CA 94502, USA
    Cerebrovasc Dis 33:80-5. 2012
    ..Gene variants associated with disease could reveal novel mechanisms. We searched for single nucleotide polymorphisms (SNPs) associated with noncardioembolic stroke (nonCES)...
  19. doi Plasma membrane-associated glycohydrolases along differentiation of murine neural stem cells
    Massimo Aureli
    Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Via Fratelli Cervi 93, 20090 Segrate, Italy
    Neurochem Res 37:1344-54. 2012
    The activities of plasma membrane associated sialidase Neu3, total β-glucosidase, CBE-sensitive β-glucosidase, non-lysosomal β-glucosyl ceramidase GBA2, β-galactosidase, β-hexosaminidase and sphingomyelinase were determined at three ..
  20. doi Mammalian sialidases: physiological and pathological roles in cellular functions
    Taeko Miyagi
    Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Japan
    Glycobiology 22:880-96. 2012
    ..Four types of mammalian sialidases have been identified and characterized to date, designated as NEU1, NEU2, NEU3 and NEU4...
  21. pmc Reduced susceptibility to colitis-associated colon carcinogenesis in mice lacking plasma membrane-associated sialidase
    Kazunori Yamaguchi
    Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, Japan
    PLoS ONE 7:e41132. 2012
    ..We previously reported that the membrane-associated mammalian sialidase NEU3, which preferentially acts on gangliosides, is involved in cell differentiation, motility, and tumorigenesis...
  22. doi MmNEU3 sialidase over-expression in C2C12 myoblasts delays differentiation and induces hypertrophic myotube formation
    Nadia Papini
    Department of Medical Chemistry, University of Milan, 20090 Milan, Italy
    J Cell Biochem 113:2967-78. 2012
    ..In order to support the role of the plasma membrane-associated sialidase NEU3 in skeletal muscle differentiation and to analyse which events of the process are mainly affected by this sialidase,..
  23. doi Sialidase occurs in both membranes of the nuclear envelope and hydrolyzes endogenous GD1a
    Jianfeng Wang
    Department of Neurology and Neurosciences, New Jersey Medical School, UMDNJ, Newark, New Jersey 07103, USA
    J Neurochem 111:547-54. 2009
    ..Western blot analysis of the separated membranes revealed occurrence of Neu3 in the inner membrane and Neu1 in the outer membrane of the NE...
  24. doi Enhancing glycoprotein sialylation by targeted gene silencing in mammalian cells
    Min Zhang
    Cell Sciences and Development, SAFC Biosciences a member of Sigma Aldrich Group, 2909 Laclede Avenue, Saint Louis, MO 63103, USA
    Biotechnol Bioeng 105:1094-105. 2010
    ..RNA (siRNA) and short-hairpin RNA (shRNA) to reduce expression of two newly identified sialidase genes, Neu1 and Neu3. By knocking down expression of Neu3 we achieved a 98% reduction in sialidase function in CHO cells...
  25. pmc Moderate strength (0.23-0.28 T) static magnetic fields (SMF) modulate signaling and differentiation in human embryonic cells
    Zhiyun Wang
    Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, USA
    BMC Genomics 10:356. 2009
    ..This study begins to bridge this gulf by investigating static magnetic fields (SMF) through global mRNA profiling in human embryonic cells coupled with software analysis to identify the affected signaling pathways...
  26. doi Down regulation of membrane-bound Neu3 constitutes a new potential marker for childhood acute lymphoblastic leukemia and induces apoptosis suppression of neoplastic cells
    Chandan Mandal
    Indian Institute of Chemical Biology, Kolkata, India
    Int J Cancer 126:337-49. 2010
    Membrane-linked sialidase Neu3 is a key enzyme for the extralysosomal catabolism of gangliosides. In this respect, it regulates pivotal cell surface events, including trans-membrane signaling, and plays an essential role in carcinogenesis...
  27. doi Activity of plasma membrane beta-galactosidase and beta-glucosidase
    Massimo Aureli
    Department of Medical Chemistry, Biochemistry and Biotechnology, Center of Excellence on Neurodegenerative Diseases, University of Milano, Segrate, Italy
    FEBS Lett 583:2469-73. 2009
    Human fibroblasts produce ceramide from sialyllactosylceramide on the plasma membranes. Sialidase Neu3 is known to be plasma membrane associated, while only indirect data suggest the plasma membrane association of beta-galactosidase and ..
  28. pmc Developmental change of sialidase neu4 expression in murine brain and its involvement in the regulation of neuronal cell differentiation
    Kazuhiro Shiozaki
    Division of Biochemistry, Miyagi Cancer Center Research Institute, Natori, Miyagi 981 1293, Japan
    J Biol Chem 284:21157-64. 2009
    ..We previously demonstrated that sialidase Neu3, also rich in mouse brain, is up-regulated during neuronal differentiation with involvement in acceleration of ..
  29. doi Plasma membrane-associated sialidase (NEU3) promotes formation of colonic aberrant crypt foci in azoxymethane-treated transgenic mice
    Kazuhiro Shiozaki
    Division of Biochemistry, Miyagi Cancer Center Research Institute, 47 1 Nodayama, Medeshima shiode, Natori, Miyagi, 981 1293, Japan
    Cancer Sci 100:588-94. 2009
    Human plasma membrane-associated sialidase (NEU3) specifically hydrolyzes gangliosides, and it is up-regulated in colon cancer and plays an essential role in the expression of malignant phenotypes...
  30. pmc NEU3 sialidase strictly modulates GM3 levels in skeletal myoblasts C2C12 thus favoring their differentiation and protecting them from apoptosis
    Luigi Anastasia
    Department of Medical Chemistry, Biochemistry, and Biotechnology, University of Milan, 20090 Milan, Italy
    J Biol Chem 283:36265-71. 2008
    Membrane-bound sialidase NEU3, often referred to as the "ganglioside sialidase," has a critical regulatory function on the sialoglycosphingolipid pattern of the cell membrane, with an anti-apoptotic function, especially in cancer cells...
  31. doi Silencing of membrane-associated sialidase Neu3 diminishes apoptosis resistance and triggers megakaryocytic differentiation of chronic myeloid leukemic cells K562 through the increase of ganglioside GM3
    C Tringali
    Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Segrate, Milan, Italy
    Cell Death Differ 16:164-74. 2009
    ..is also blocked because of low levels of ganglioside GM3, derived by the high expression of sialidase Neu3 active on GM3...
  32. doi Protein sialylation by sialyltransferase involves radiation resistance
    Minyoung Lee
    Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
    Mol Cancer Res 6:1316-25. 2008
    ..Inhibition of sialylation by transfection with neuraminidase 2 or neuraminidase 3 or by treatment with short interfering RNA targeting ST6Gal I reversed the effects of ST6Gal I overexpression...
  33. pmc Limited inhibitory effects of oseltamivir and zanamivir on human sialidases
    Keiko Hata
    Division of Biochemistry, Miyagi Cancer Center Research Institute, Natori 981 1293, Japan
    Antimicrob Agents Chemother 52:3484-91. 2008
    ..the activities of any of the sialidases, even at 1 mM, while zanamivir significantly inhibited the human sialidases NEU3 and NEU2 in the micromolar range (K(i), 3.7 +/- 0.48 and 12.9 +/- 0...
  34. doi Thymoquinone from nutraceutical black cumin oil activates Neu4 sialidase in live macrophage, dendritic, and normal and type I sialidosis human fibroblast cells via GPCR Galphai proteins and matrix metalloproteinase-9
    Trisha M Finlay
    Department of Microbiology and Immunology, Queen s University, Kingston, ON, K7L3N6, Canada
    Glycoconj J 27:329-48. 2010
    ..RT-PCR and western blot analyses reveal no correlation between mRNA and protein values for Neu3 and Neu4 in human monocytic THP-1 cells, suggesting for the first time a varied post-transcriptional mechanism for ..
  35. pmc A crucial role of sialidase Neu1 in hyaluronan receptor function of CD44 in T helper type 2-mediated airway inflammation of murine acute asthmatic model
    S Katoh
    Department of Cell Regulation, Faculty of Medicine, Kagawa University, Kanagawa, Japan
    Clin Exp Immunol 161:233-41. 2010
    ..Splenic CD4+ T cell binding of HA was examined with flow cytometry. Expression of sialidases (Neu1, Neu2, Neu3 and Neu4) in spleen cells was evaluated by quantitative real-time reverse transcription-polymerase chain reaction...
  36. doi Insight into substrate recognition and catalysis by the human neuraminidase 3 (NEU3) through molecular modeling and site-directed mutagenesis
    Amgad Albohy
    Alberta Ingenuity Centre for Carbohydrate Science, Department of Chemistry, University of Alberta, Edmonton, Alberta T6G2G2, Canada
    Glycobiology 20:1127-38. 2010
    ..Members of the family, such as NEU2 and NEU1, are cytosolic or lysosomal, while NEU3 and NEU4 are membrane-associated...
  37. ncbi Asymmetric membrane ganglioside sialidase activity specifies axonal fate
    Jorge Santos Da Silva
    Cavalieri Ottolenghi Scientific Institute, University of Turin, 10043 Orbassano, Turin, Italy
    Nat Neurosci 8:606-15. 2005
    ..Here we show that plasma membrane ganglioside sialidase (PMGS) asymmetrically accumulates at the tip of one neurite of the unpolarized rat neuron, inducing actin ..
  38. doi Membrane sialidase NEU3 is highly expressed in human melanoma cells promoting cell growth with minimal changes in the composition of gangliosides
    Maiko Miyata
    Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Aichi, Japan
    Cancer Sci 102:2139-49. 2011
    NEU3 is a membrane sialidase specific for gangliosides. Its increased expression and implication in some cancers have been reported. Here, we analyzed NEU3 expression in malignant melanoma cell lines and its roles in the cancer phenotypes...
  39. pmc Gallus gallus NEU3 sialidase as model to study protein evolution mechanism based on rapid evolving loops
    Edoardo Giacopuzzi
    Department of Biomedical Sciences and Biotechnology, Unit of Biology and Genetics, University of Brescia, Viale Europa 11, Brescia 25123, Italy
    BMC Biochem 12:45. 2011
    ..These features prompted us to extend our studies on this protein family in birds, to get insights on the evolution of this class of glycohydrolases...
  40. pmc Plasma membrane-associated sialidase (NEU3) regulates progression of prostate cancer to androgen-independent growth through modulation of androgen receptor signaling
    S Kawamura
    Department of Urology, Miyagi Cancer Center, Natori, Japan
    Cell Death Differ 19:170-9. 2012
    ..treatments for androgen-independent prostate cancer, we have investigated plasma membrane-associated sialidase (NEU3), the key enzyme for ganglioside hydrolysis participating in transmembrane signaling...
  41. doi Substrate recognition of the membrane-associated sialidase NEU3 requires a hydrophobic aglycone
    Mahendra S Sandbhor
    Alberta Ingenuity Centre for Carbohydrate Science, Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada
    Biochemistry 50:6753-62. 2011
    ..The NEU3 isoform is a membrane-associated enzyme that cleaves glycolipid substrates...
  42. doi Differentially regulated expression of 9-O-acetyl GD3 (CD60b) and 7-O-acetyl-GD3 (CD60c) during differentiation and maturation of human T and B lymphocytes
    Dirk Wipfler
    German Cancer Research Center, D015 Translational Immunology, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Glycobiology 21:1161-72. 2011
    ..the key enzyme for GD3 synthesis, was highest in tonsillar T cells, whereas transcriptional levels of sialidase NEU3 and O-acetylesterase H-Lse were lowest in activated T cells...
  43. doi Inhibitor selectivity of a new class of oseltamivir analogs against viral neuraminidase over human neuraminidase enzymes
    Amgad Albohy
    Alberta Ingenuity Centre for Carbohydrate Science, Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
    Bioorg Med Chem 19:2817-22. 2011
    ..influenza group-1 neuraminidase enzyme (N1 subtype) against recombinant forms of the human neuraminidase enzymes NEU3 and NEU4...
  44. doi Cell surface sphingolipid glycohydrolases in neuronal differentiation and aging in culture
    Massimo Aureli
    Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Milano, Italy
    J Neurochem 116:891-9. 2011
    ..I, II and IV, sialidase, β-galactosidase and β-glucosidase, and the PM-associated activities of sialidase Neu3, β-galactosidase, Conduritol B Epoxide-sensitive β-glucosidase and β-glucosidase GBA2 in rat cerebellar granule ..
  45. pmc LPS-induced cytokine production in human dendritic cells is regulated by sialidase activity
    Nicholas M Stamatos
    University of Maryland Medical Center, 725 West Lombard St, Baltimore, MD 21201, USA
    J Leukoc Biol 88:1227-39. 2010
    ..Of the four genetically distinct sialidases (Neu1-4), Neu1, Neu3, and Neu4 are expressed in human monocytes, but only Neu1 and Neu3 are up-regulated as cells differentiate into DCs...
  46. doi Sialidases in vertebrates: a family of enzymes tailored for several cell functions
    Eugenio Monti
    Department of Biomedical Science and Biotechnology, University of Brescia, Italy
    Adv Carbohydr Chem Biochem 64:403-79. 2010
    ..they are the lysosomal (NEU1), the cytosolic (NEU2), and plasma membrane- and intracellular-associated sialidases (NEU3 and NEU4). The molecular cloning of several mammalian sialidases since 1993 has boosted research in this field...
  47. doi Disialoganglioside GD3 synthase expression recruits membrane transglutaminase 2 during erythroid differentiation of the human chronic myelogenous leukemia K562 cells
    Sung Koo Kang
    Molecular and Cellular Glycobiology Unit, Department of Biological Science, Sungkyunkwan University, Suwon, Kyunggi Do, Korea
    Proteomics 8:3317-28. 2008
    ..level was increased in GD3 synthase-transfected cells compared with vector- and plasma membrane-associated ganglioside sialidase (Neu3)-transfected cells...
  48. doi Human sialidase as a cancer marker
    Taeko Miyagi
    Division of Biochemistry, Miyagi Cancer Center Research Institute, Natori, Miyagi, Japan
    Proteomics 8:3303-11. 2008
    ..Immunohistochemistry of cancer tissues using the antibody against the plasma membrane sialidase was useful for clinical diagnosis...
  49. pmc Plasma-membrane-associated sialidase (NEU3) differentially regulates integrin-mediated cell proliferation through laminin- and fibronectin-derived signalling
    Kengo Kato
    Division of Biochemistry, Miyagi Cancer Center Research Institute, Natori 981 1293, Japan
    Biochem J 394:647-56. 2006
    We have found previously that human plasma-membrane-associated sialidase (NEU3), a key glycosidase for ganglioside degradation, was markedly up-regulated in human colon cancers, with an involvement in suppression of apoptosis...
  50. ncbi Differential expression of endogenous sialidases of human monocytes during cellular differentiation into macrophages
    Nicholas M Stamatos
    Institute of Human Virology, University of Maryland, Baltimore, MD 21201, USA
    FEBS J 272:2545-56. 2005
    ..this study, we demonstrate that three of these sialidases, lysosomal Neu1 and Neu4 and plasma membrane-associated Neu3, are expressed in human monocytes...
  51. ncbi Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells
    Volkan Seyrantepe
    Department of Medical Genetics, Sainte Justine Hospital, University of Montreal, 3175 Cote Ste Catherine, Montreal, Quebec H3T 1C5, Canada
    J Biol Chem 279:37021-9. 2004
    ..have been described as follows: lysosomal (Neu1, gene NEU1), cytoplasmic (Neu2, gene NEU2), and plasma membrane (Neu3, gene NEU3)...
  52. ncbi Molecular characterization of membrane type and ganglioside-specific sialidase (Neu3) expressed in E. coli
    Ki Tae Ha
    National Research Laboratory for Glycobiology, Ministry of Science and Technology, Korean Government
    Mol Cells 17:267-73. 2004
    Endogenous expression of human membrane type ganglioside sialidase (Neu3) was examined in various cell lines including NB-1, U87MG, SK-MEL-2, SK-N-MC, HepG2, Hep3B, Jurkat, HL-60, K562, ECV304, Hela and MCF-7...
  53. ncbi Molecular cloning and characterization of NEU4, the fourth member of the human sialidase gene family
    E Monti
    Department of Biomedical Science and Biotechnology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
    Genomics 83:445-53. 2004
    ..unique among mammalian sialidases, shows a high degree of homology for NEU2 and the plasma membrane-associated (NEU3) sialidases. RNA dot-blot analysis showed a low but wide expression pattern, with the highest level in liver...
  54. ncbi Identification and expression of Neu4, a novel murine sialidase
    Elena M Comelli
    The Scripps Research Institute, Department of Molecular Biology, MEM L71, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Gene 321:155-61. 2003
    ..Of the other known murine sialidases, it is most similar to Neu3 (42%)...
  55. ncbi Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells
    Jurgen Kopitz
    Institut für Molekulare Pathologie, Klinikum der Ruprecht Karls Universtiät, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany
    Oncogene 22:6277-88. 2003
    ..On the surface of neuroblastoma cells (SK-N-MC), the increased GM1 density, a result of upregulated ganglioside sialidase activity, is a key factor for the switch from proliferation to differentiation...
  56. ncbi Overexpression of plasma membrane-associated sialidase attenuates insulin signaling in transgenic mice
    Akinori Sasaki
    Division of Biochemistry, Miyagi Prefectural Cancer Center, Natori, Miyagi 981 1293, Japan
    J Biol Chem 278:27896-902. 2003
    ..Here we demonstrate that mice overexpressing the human ortholog (NEU3) develop diabetic phenotype by 18-22 weeks associated with hyperinsulinemia, islet hyperplasia, and increased beta-..
  57. ncbi Substrate specificity and inhibitor studies of a membrane-bound ganglioside sialidase isolated from human brain tissue
    Christian Oehler
    Institute of Pathochemistry and Neurochemistry, University of Heidelberg, Im Neuenheimer Feld 220 221, D 69120 Heidelberg, Germany
    Biol Chem 383:1735-42. 2002
    ..Here we report on the specificity toward gangliosides and susceptibility to certain inhibitors of a ganglioside sialidase solubilized and purified 5100-fold from human brain...
  58. ncbi A close association of the ganglioside-specific sialidase Neu3 with caveolin in membrane microdomains
    Yan Wang
    Division of Biochemistry, Research Institute, Miyagi Prefectural Cancer Center, Natori, Miyagi 981 1293, Japan
    J Biol Chem 277:26252-9. 2002
    The ganglioside-specific sialidase Neu3 has been suggested to play essential roles in regulation of cell surface functions because of its major localization in the plasma membrane and strict substrate preference for gangliosides involved ..
  59. ncbi Desialylation of extracellular GD1a-neoganglioprotein suggests cell surface orientation of the plasma membrane-bound ganglioside sialidase activity in human neuroblastoma cells
    J Kopitz
    University of Heidelberg, Department of Pathochemistry and Neurochemistry, Im Neuenheimer Feld 220, D 69120, Heidelberg, Germany
    FEBS Lett 491:233-6. 2001
    ..We conclude that the ganglioside sialidase activity is cell surface-orientated and displays an in situ specificity that mirrors enzyme preparations ..
  60. pmc Identification and expression of NEU3, a novel human sialidase associated to the plasma membrane
    E Monti
    Telethon Institute of Genetics and Medicine TIGEM, San Raffaele Biomedical Science Park, Via Olgettina 58, 20132 Milan, Italy and Department of Biomedical Science and Biotechnology, University of Brescia, Via Valsabbina 19, 25123 Brescia, Italy
    Biochem J 349:343-51. 2000
    ..Here we describe the identification and expression of a human plasma-membrane-associated sialidase, NEU3, isolated starting from an expressed sequence tag (EST) clone...
  61. ncbi Cloning, expression, and chromosomal mapping of a human ganglioside sialidase
    T Wada
    Research Institute, Miyagi Prefectural Cancer Center, Natori, Miyagi, 981 1293, Japan
    Biochem Biophys Res Commun 261:21-7. 1999
    Here we report the cDNA sequence of a human ganglioside sialidase. The cDNA was isolated from a human brain cDNA library by screening with a 240 bp probe generated by polymerase chain reaction using primers based on the sequences of rat ..
  62. ncbi Protective protein in the bovine lysosomal beta-galactosidase complex
    M Hiraiwa
    Department of Neurosciences, Center for Molecular Genetics, University of California at San Diego, La Jolla 92093 0634, USA
    Biochim Biophys Acta 1341:189-99. 1997
    ..Both beta-galactosidase and cathepsin A activities were labile under the dissociated condition, indicating that it physiologically stabilizes not only beta-galactosidase but also itself by forming the complex...
  63. pmc Infectivities of human and other primate lentiviruses are activated by desialylation of the virion surface
    H Hu
    Department of Viral Infection, Institute of Medical Science, University of Tokyo, Minato ku, Japan
    J Virol 70:7462-70. 1996
    ..Thus, the sialylation catalyzed by host cell pathways appeared to reduce the infectivity of human and nonhuman primate lentiviruses. Our results further suggested that desialylation would help increase the titers of HIV-based vectors...
  64. ncbi Role of plasma membrane ganglioside sialidase of human neuroblastoma cells in growth control and differentiation
    J Kopitz
    Institute of Pathochemistry and General Neurochemistry, University of Heidelberg, Germany
    Biochem Biophys Res Commun 199:1188-93. 1994
    ..The results suggest an important role of the ganglioside sialidase of the plasma membrane in the processes of proliferation control and differentiation in this neuronal cell ..
  65. ncbi Homology modeling of human sialidase enzymes NEU1, NEU3 and NEU4 based on the crystal structure of NEU2: hints for the design of selective NEU3 inhibitors
    Sadagopan Magesh
    Department of Applied Bioorganic Chemistry, Gifu University, Gifu 501 1193, Japan
    J Mol Graph Model 25:196-207. 2006
    ..according to their major intracellular location as intralysomal (NEU1), cytosolic (NEU2), plasma membrane (NEU3) and lysosomal or mitochondrial membrane (NEU4) associated sialidases...
  66. ncbi Plasma membrane-associated sialidase is up-regulated in renal cell carcinoma and promotes interleukin-6-induced apoptosis suppression and cell motility
    Seiji Ueno
    Division of Biochemistry, Miyagi Cancer Center Research Institute, Natori, 981 1293, Japan
    J Biol Chem 281:7756-64. 2006
    Human plasma membrane-associated sialidase (NEU3), specifically hydrolyzing gangliosides, plays crucial roles in the regulation of cell surface functions...
  67. ncbi Epidermal growth factor-induced mobilization of a ganglioside-specific sialidase (NEU3) to membrane ruffles
    Kazunori Yamaguchi
    Division of Biochemistry, Miyagi Cancer Center Research Institute, Natori, Japan
    Biochem Biophys Res Commun 346:484-90. 2006
    Human ganglioside-specific sialidase, NEU3, localized at cell membranes is thought to regulate various biological processes at cell surfaces...
  68. doi Plasma membrane-associated sialidase as a crucial regulator of transmembrane signalling
    Taeko Miyagi
    Division of Biochemistry, Miyagi Cancer Center Research Institute, Natori, 981 1293, and CREST, JST, Japan
    J Biochem 144:279-85. 2008
    ..Among those forms identified to date, plasma membrane-associated sialidase, Neu3, is a key enzyme in degradation of gangliosides, for which it exhibits a special substrate preference...
  69. doi Membrane type sialidase inhibits the megakaryocytic differentiation of human leukemia K562 cells
    Un Ho Jin
    Molecular and Cellular Glycobiology Unit, Department of Biological Science, Sungkyunkwan University, Chunchun Dong 300, Suwon, Kyunggi Do 440 746, South Korea
    Biochim Biophys Acta 1780:757-63. 2008
    The membrane type sialidase (Neu3) has been suggested to participate in cell growth, migration and differentiation...
  70. ncbi Over-expression of mammalian sialidase NEU3 reduces Newcastle disease virus entry and propagation in COS7 cells
    Luigi Anastasia
    Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Milan, Italy
    Biochim Biophys Acta 1780:504-12. 2008
    ..pattern determined by over-expression of the mammalian plasma-membrane associated, ganglioside specific, sialidase NEU3 would affect the virus-host cell interactions...
  71. ncbi Roles of plasma membrane-associated sialidase NEU3 in human cancers
    Taeko Miyagi
    Biochemistry Division, Miyagi Cancer Center Research Institute, 47 1 Nodayama, Medeshima shiode, Natori, Miyagi, 981 1293, Japan
    Biochim Biophys Acta 1780:532-7. 2008
    ..Among human sialidases so far identified, sialidase NEU3 is a key enzyme for ganglioside degradation because of its uniqueness both in its localization in the plasma ..
  72. ncbi Enhanced expression of membrane-associated sialidase Neu3 decreases GD3 and increases GM3 on the surface of Jurkat cells during etoposide-induced apoptosis
    Yutaro Azuma
    Department of Clinical Chemistry, School of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274 8510, Japan
    Biol Pharm Bull 30:1680-4. 2007
    ..N-acetylneuraminic acid and measured the mRNA expression of the plasma membrane-associated sialidase Neu3 and the lysozomal Neu1 using real-time PCR...
  73. pmc Molecular cloning and biochemical characterization of sialidases from zebrafish (Danio rerio)
    Marta Manzoni
    Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
    Biochem J 408:395-406. 2007
    ..genes are organized in clusters located on chromosome 21 and are all more closely related to mammalian sialidase NEU3. They were thus named neu3.1, neu3.2, neu3.3, neu3.4 and neu3.5...
  74. pmc Sialidase NEU3 is a peripheral membrane protein localized on the cell surface and in endosomal structures
    Gabriele Zanchetti
    Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
    Biochem J 408:211-9. 2007
    Sialidase NEU3 is also known as the plasma-membrane-associated form of mammalian sialidases, exhibiting a high substrate specificity towards gangliosides...
  75. ncbi Overexpression of membrane sialic acid-specific sialidase Neu3 inhibits matrix metalloproteinase-9 expression in vascular smooth muscle cells
    Sung Kwon Moon
    Molecular and Cellular Glycobiology Unit, Department of Biological Science, Sungkyunkwan University, Chunchun Dong 300, Suwon City, Kyunggi Do 440 746, Republic of Korea
    Biochem Biophys Res Commun 356:542-7. 2007
    The ganglioside-specific sialidase Neu3 has been suggested to participate in cell growth, migration, and differentiation...
  76. ncbi A crucial role of plasma membrane-associated sialidase in the survival of human cancer cells
    T Wada
    Division of Biochemistry, Miyagi Cancer Center Research Institute, Natori, Miyagi, Japan
    Oncogene 26:2483-90. 2007
    Human plasma membrane-associated sialidase (NEU3), a key enzyme for ganglioside degradation, is markedly upregulated in human cancers, leading to apoptosis suppression...
  77. ncbi Monocyte differentiation up-regulates the expression of the lysosomal sialidase, Neu1, and triggers its targeting to the plasma membrane via major histocompatibility complex class II-positive compartments
    Feng Liang
    Sainte Justine Hospital and the Department of Pediatrics, University of Montreal, Montreal, Quebec H3T 1C5, Canada
    J Biol Chem 281:27526-38. 2006
    ..In contrast to other cellular sialidases Neu2, Neu3, and Neu4, whose expression either remains unchanged or is down-regulated, Neu1 mRNA, protein and activity are ..
  78. ncbi Sialidase expression in activated human T lymphocytes influences production of IFN-gamma
    Xinli Nan
    Institute of Human Biology, and Department of Medicine, University of Maryland Medical Center, 725 West Lombard Street, Baltimore, MD 21201, USA
    J Leukoc Biol 81:284-96. 2007
    ..In this study, we demonstrate that only lysosomal Neu1 and plasma membrane-associated Neu3 are detected in freshly isolated and activated human T lymphocytes...
  79. ncbi Lysosomal and plasma membrane ganglioside GM3 sialidases of cultured human fibroblasts. Differentiation by detergents and inhibitors
    H R Schneider-Jakob
    Institut für Pathochemie und Allgemeine Neurochemie, Universitat Heidelberg
    Biol Chem Hoppe Seyler 372:443-50. 1991
    ..both activities were normal in fibroblasts from patients with mucolipidosis IV, previously thought to be a ganglioside sialidase deficiency disorder...
  80. ncbi Modification of sialidase levels and sialoglycoconjugate pattern during erythroid and erytroleukemic cell differentiation
    Cristina Tringali
    Department of Medical Chemistry, Biochemistry and Biotechnology, Faculty of Exercise Science, University of Milan, LITA Segrate, Via Fratelli Cervi 93, 20090 Segrate, Milan, Italy
    Glycoconj J 24:67-79. 2007
    ..Herein we show that only the lysosomal sialidase Neu1 and the plasma membrane-associated sialidase Neu3 are expressed in CFU-E erythroid precursors and K562 erythroleukemic cells...
  81. ncbi Induction of axonal differentiation by silencing plasma membrane-associated sialidase Neu3 in neuroblastoma cells
    Rea Valaperta
    Department of Medical Chemistry, Biochemistry and Biotechnology, and Center of Excellence on Neurodegenerative Diseases, University of Milan, Segrate, Italy
    J Neurochem 100:708-19. 2007
    A reduction of 70% of the plasma membrane-associated sialidase Neu3 activity, due to a corresponding reduction of the enzyme expression by transducing cells with a short hairpin RNA encoding a sequence target (complementary messenger of ..
  82. ncbi Down-regulation of sialidase NEU4 may contribute to invasive properties of human colon cancers
    Hideaki Yamanami
    Division of Biochemistry, Miyagi Cancer Center Research Institute, Miyagi Cancer Center, 47 1 Nodayama, Medeshima shiode, Natori, Miyagi, 981 1293, Japan
    Cancer Sci 98:299-307. 2007
    ..We previously demonstrated that a human sialidase associated with plasma membranes (NEU3) is up-regulated in human colon cancer and is involved in suppression of apoptosis...
  83. pmc Up-regulation of plasma membrane-associated ganglioside sialidase (Neu3) in human colon cancer and its involvement in apoptosis suppression
    Yoichiro Kakugawa
    Division of Biochemistry, Research Institute, Department of Surgery, Miyagi Prefectural Cancer Center, Natori, Miyagi 981 1293, Japan
    Proc Natl Acad Sci U S A 99:10718-23. 2002
    Human plasma membrane-associated sialidase (Neu3) is unique in specifically hydrolyzing gangliosides, thought to participate in cell differentiation and transmembrane signaling, thereby playing crucial roles in the regulation of cell ..
  84. ncbi Increased hepatic expression of ganglioside-specific sialidase, NEU3, improves insulin sensitivity and glucose tolerance in mice
    Shinsuke Yoshizumi
    Department of Metabolism and Diabetes, Tohoku University School of Medicine, Sendai 980 8574, Japan
    Metabolism 56:420-9. 2007
    ..Plasma membrane-associated sialidase, NEU3, is a key enzyme for ganglioside hydrolysis...
  85. pmc CD15 expression in human myeloid cell differentiation is regulated by sialidase activity
    Samah Zeineb Gadhoum
    Department of Dermatology, Brigham and Women s Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA
    Nat Chem Biol 4:751-7. 2008
    ..Our results unveil a new paradigm by demonstrating a critical role for post-Golgi membrane glycosidase activity in the 'biosynthesis' of a key glycan determinant...

Research Grants25

  1. Role of Sialidase in Pulmonary Host Defenses and Acute Lung Injury
    Alan Cross; Fiscal Year: 2009
    ..hypothesis, we propose the following: In Specific Aim 1 we will define which form(s) of PMN sialidase(s) (neul and neu3) regulates adherence to and migration across human lung microvascular EC by overexpression and knockdown of ..
  2. Role of Sialidase in Pulmonary Host Defenses and Acute Lung Injury
    Alan Cross; Fiscal Year: 2010
    ..hypothesis, we propose the following: In Specific Aim 1 we will define which form(s) of PMN sialidase(s) (neul and neu3) regulates adherence to and migration across human lung microvascular EC by overexpression and knockdown of ..
  3. Role of Sialidase in Pulmonary Host Defenses and Acute Lung Injury
    Alan Cross; Fiscal Year: 2007
    ..hypothesis, we propose the following: In Specific Aim 1 we will define which form(s) of PMN sialidase(s) (neul and neu3) regulates adherence to and migration across human lung microvascular EC by overexpression and knockdown of ..
  4. Role of Nuclear Gangliosides in Neuronal Function
    Robert Ledeen; Fiscal Year: 2007
    ..Demonstrated attenuation of such seizures by administered LIGA-20, a membrane-permeant derivative of GM1, will be further studied by determining the role of nuclear GM1/exchanger in modulating the seizure mechanism. ..
  5. Role of Nuclear Gangliosides in Neuronal Function
    Robert Ledeen; Fiscal Year: 2009
    ..Demonstrated attenuation of such seizures by administered LIGA-20, a membrane-permeant derivative of GM1, will be further studied by determining the role of nuclear GM1/exchanger in modulating the seizure mechanism. ..
  6. Nuclear GM1 Ganglioside in Neuronal Differentiation
    Robert Ledeen; Fiscal Year: 2004
    ..CGN from the knockouts will be subjected to glutamate as an alternative means of elevating [CA2+]i. A stroke model will also be employed. ..
  7. Role of Cellular Sialidase in Pathogenesis of HIV-1
    Nicholas Stamatos; Fiscal Year: 2004
    ..abstract_text> ..
  8. NUCLEAR GM1--ROLE IN NEURONAL DIFFERENTATION
    Robert Ledeen; Fiscal Year: 2000
    ..GM1 as a general aspect of process outgrowth in the nervous system? (f) Does this upregulation of nuclear GM1 persist into maturity, or is it a specific feature of development? (g) What is the behavior of nuclear GM1 during regeneration? ..
  9. Role of Nuclear Gangliosides in Neuronal Function
    Robert W Ledeen; Fiscal Year: 2010
    ..In addition to analyzing GM1 levels in brain samples from PD patients, we will study the mechanistic role of GM1 using the above genetically modified mice and N27 cells. ..