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Cited by 76Lysosomal Storage Disorders ResearchGlycogen Storage Diseases and MyoclonusGlycosylation and Glycoproteins Research

Pathogenesis, emerging therapeutic targets and treatment in sialidosis

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D’Azzo, Alessandra, Machado, Eda, Annunziata, Ida·2015·Expert Opinion on Orphan Drugs
DOI 10.1517/21678707.2015.1025746PMC PMC4777310
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Abstract

INTRODUCTION: gene, encoding the lysosomal sialidase NEU1. Deficient enzyme activity results in impaired processing/degradation of sialo-glycoproteins, and accumulation of oversialylated metabolites. Sialidosis is considered an orphan disorder for which no therapy is currently available. AREAS COVERED: mutations so far identified; NEU1 requirement to complex with the protective protein/cathepsin A for stability and activation; and the pathogenic effects of NEU1 deficiency. Studies of the molecular mechanisms of pathogenesis in animal models uncovered basic cellular pathways downstream of NEU1 and its substrates, which may be implicated in more common adult (neurodegenerative) diseases. The development of a Phase I/II clinical trial for patients with galactosialidosis may prove suitable for sialidosis patients with the attenuated form of the disease. EXPERT OPINION: Recently, there has been a renewed interest in the development of therapies for orphan LSDs, like sialidosis. Given the small number of potentially eligible patients, the way to treat sialidosis would be through the coordinated effort of clinical centers, which provide diagnosis and care for these patients, and the basic research labs that work towards understanding the disease pathogenesis.

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  • NEU1 is a ubiquitously expressed mammalian sialidase located in lysosomes and on the cell membrane.

    “The ubiquitously expressed NEU1 is the most abundant homolog, shares the least sequence similarity with its family members, and is active on oligosaccharides, glycopeptides, and glycoproteins (1, 12–16). It is located in lysosomes and on the cell surface (12, 14, 15, 17, 18).”

    From Structure of the immunoregulatory sialidase NEU1 (2023) · cites this paper as [16]

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  1. [1]Bonten E van der Spoel A Fornerod M Grosveld G d'Azzo A Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis Genes & development 1996 12 15 10 24 3156 3169 8985184 ** This paper describes the cloning of the human lysosomal neuraminidase NEU1.
  2. [2]Pshezhetsky AV Richard C Michaud L Igdoura S Wang S Elsliger MA Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis Nature genetics 1997 3 15 3 316 320 9054950
  3. [3]Durand P Gatti R Cavalieri S Borrone C Tondeur M Michalski JC Sialidosis (mucolipidosis I) Helvetica paediatrica acta 1977 11 32 4–5 391 400 617984 * This is the first report referring to NEU1 deficiency as sialidosis.
  4. [4]Cantz M Gehler J Spranger J Mucolipidosis I: increased sialic acid content and deficiency of an alpha-N-acetylneuraminidase in cultured fibroblasts Biochemical and biophysical research communications 1977 1 24 74 2 732 738 836321
  5. [5]Lowden JA O'Brien JS Sialidosis: a review of human neuraminidase deficiency American journal of human genetics 1979 1 31 1 1 18 107795 PMC1685665
  6. [6]Thomas G The Online Metabolic & Molecular Bases of Inherited Diseases 2013 New York McGraw-Hill Publishing Co.
  7. [7]d'Azzo A Bonten E Molecular mechanisms of pathogenesis in a glycosphingolipid and a glycoprotein storage disease Biochem Soc Trans 2010 12 38 6 1453 1457 21118106 PMC3129614
  8. [8]Caciotti A Di Rocco M Filocamo M Grossi S Traverso F d'Azzo A Type II sialidosis: review of the clinical spectrum and identification of a new splicing defect with chitotriosidase assessment in two patients Journal of neurology 2009 11 256 11 1911 1915 19568825 * This is a recent comprehensive review of mutations occurring in Type II sialidosis.
  9. [9]Takahashi Y Nakamura Y Yamaguchi S Orii T Urinary oligosaccharide excretion and severity of galactosialidosis and sialidosis Clinica chimica acta; international journal of clinical chemistry 1991 12 16 203 2–3 199 210 1777981
  10. [10]Canafoglia L Robbiano A Pareyson D Panzica F Nanetti L Giovagnoli AR Expanding sialidosis spectrum by genome-wide screening: NEU1 mutations in adult-onset myoclonus Neurology 2014 Jun 3 82 22 2003 2006 24808020 ** This paper shows that sialidosis should be suspected in adult patients with isolated action myoclonus carrying NEU1 mutations without additional clinical signs of sialidosis.
  11. [11]Muona M Berkovic SF Dibbens LM Oliver KL Maljevic S Bayly MA A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy Nature genetics 2014 11 17 PMC4281260 25401298
  12. [12]Sobral I Cachulo Mda L Figueira J Silva R Sialidosis type I: ophthalmological findings BMJ case reports 2014 2014 PMC4202095 25323282
  13. [13]Loren DJ Campos Y d'Azzo A Wyble L Grange DK Gilbert-Barness E Sialidosis presenting as severe nonimmune fetal hydrops is associated with two novel mutations in lysosomal alpha-neuraminidase Journal of perinatology: official journal of the California Perinatal Association 2005 7 25 7 491 494 15908988
  14. [14]Lee BH Kim YM Kim JH Kim GH Lee BS Kim CJ Histological, biochemical, and genetic characterization of early-onset fulminating sialidosis type 2 in a Korean neonate with hydrops fetalis Brain & development 2014 2 36 2 171 175 23433491
  15. [15]Rosenberg R Halimi E Mention-Mulliez K Cuisset JM Holder M Defoort-Dhellemmes S Five year follow-up of two sisters with type II sialidosis: systemic and ophthalmic findings including OCT analysis Journal of pediatric ophthalmology and strabismus 2013 50 e33 e36 Online 23819954
  16. [16]Bonten EJ Annunziata I d'Azzo A Lysosomal multienzyme complex: pros and cons of working together Cellular and molecular life sciences: CMLS 2014 6 71 11 2017 2032 24337808 PMC4037752
  17. [17]d'Azzo A Andria G Bonten E Annunziata I The Online Metabolic & Molecular Bases of Inherited Diseases 2013 New York McGraw-Hill Publishing Co. * This chapter includes the most up to date information on the clinical,molecular and biochemical aspects of Galactosialidosis.
  18. [18]Varki A Schauer R Varki A Cummings RD Esko JD Freeze HH Stanley P Bertozzi CR Sialic Acids Essentials of Glycobiology 2009 2nd ed. NY Cold Spring Harbor 20301239
  19. [19]Monti E Bonten E D'Azzo A Bresciani R Venerando B Borsani G Sialidases in vertebrates: a family of enzymes tailored for several cell functions Advances in carbohydrate chemistry and biochemistry 2010 64 403 479 20837202
  20. [20]Miyagi T Yamaguchi K Mammalian sialidases: physiological and pathological roles in cellular functions Glycobiology 2012 7 22 7 880 896 22377912 References 19 and 20 are comprehensive review describing the properties and functions of mammalian sialidases
  21. [21]Giacopuzzi E Bresciani R Schauer R Monti E Borsani G New insights on the sialidase protein family revealed by a phylogenetic analysis in metazoa PloS one 2012 7 8 e44193 22952925 PMC3431349
  22. [22]Smutova V Albohy A Pan X Korchagina E Miyagi T Bovin N Structural basis for substrate specificity of mammalian neuraminidases PloS one 2014 9 9 e106320 25222608 PMC4164519
  23. [23]Bonten EJ Campos Y Zaitsev V Nourse A Waddell B Lewis W Heterodimerization of the sialidase NEU1 with the chaperone protective protein/cathepsin A prevents its premature oligomerization J Biol Chem 2009 Oct 9 284 41 28430 28441 19666471 PMC2788892 ** This paper identifies binding sites on NEU1 and PPCA responsible for their interaction and proposes a novel mechanism of binding between the two proteins.
  24. [24]Lukong KE Seyrantepe V Landry K Trudel S Ahmad A Gahl WA Intracellular distribution of lysosomal sialidase is controlled by the internalization signal in its cytoplasmic tail J Biol Chem 2001 Dec 7 276 49 46172 46181 11571282 * This paper identofies a C-terminal peptide in NEU1 that targets the protein to the membrane.
  25. [25]Lukong KE Elsliger MA Chang Y Richard C Thomas G Carey W Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex Hum Mol Genet 2000 4 12 9 7 1075 1085 10767332
  26. [26]Bonten EJ Arts WF Beck M Covanis A Donati MA Parini R Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis Hum Mol Genet 2000 9 18 2715 2725 11063730
  27. [27]Itoh K Naganawa Y Matsuzawa F Aikawa S Doi H Sasagasako N Novel missense mutations in the human lysosomal sialidase gene in sialidosis patients and prediction of structural alterations of mutant enzymes Journal of human genetics 2002 47 1 29 37 11829139
  28. [28]Lee YJ Son SK Park JH Song JS Cheon CK NEU1 Mutation in a Korean Infant with Type 2 Sialidosis Presenting as Isolated Fetal Ascites Pediatrics and neonatology 2014 9 12 25223955
  29. [29]Penzel R Uhl J Kopitz J Beck M Otto HF Cantz M Splice donor site mutation in the lysosomal neuraminidase gene causing exon skipping and complete loss of enzyme activity in a sialidosis patient FEBS letters 2001 Jul 20 501 2–3 135 138 11470272
  30. [30]Ranganath P Sharma V Danda S Nandineni MR Dalal AB Novel mutations in the neuraminidase-1 (NEU1) gene in two patients of sialidosis in India The Indian journal of medical research 2012 12 136 6 1048 1050 23391804 PMC3612311
  31. [31]de Geest N Bonten E Mann L de Sousa-Hitzler J Hahn C d'Azzo A Systemic and neurologic abnormalities distinguish the lysosomal disorders sialidosis and galactosialidosis in mice Hum Mol Genet 2002 Jun 1 11 12 1455 1464 12023988 ** This paper describes the first mouse model of sialidosis.
  32. [32]Zanoteli E van de Vlekkert D Bonten EJ Hu H Mann L Gomero EM Muscle degeneration in neuraminidase 1-deficient mice results from infiltration of the muscle fibers by expanded connective tissue Biochim Biophys Acta 2010 Jul-Aug 1802 7–8 659 672 20388541 PMC2906380
  33. [33]Annunziata I Patterson A Helton D Hu H Moshiach S Gomero E Lysosomal NEU1 deficiency affects amyloid precursor protein levels and amyloid-beta secretion via deregulated lysosomal exocytosis Nature communications 2013 4 2734 PMC4015463 24225533 ** This paper describes the realease of amyloidogenic peptides via lysosomal exocytosis in the mouse model of sialidosis.
  34. [34]Bonten EJ Yogalingam G Hu H Gomero E van de Vlekkert D d'Azzo A Chaperone-mediated gene therapy with recombinant AAV-PPCA in a new mouse model of type I sialidosis Biochim Biophys Acta 2013 10 1832 10 1784 1792 23770387 PMC3794473 ** This report suggests that at least some of the NEU1 mutations in type I sialidosis patients respond to treatment with PPCA.
  35. [35]Zhou XY Morreau H Rottier R Davis D Bonten E Gillemans N Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells Genes & development 1995 Nov 1 9 21 2623 2634 7590240
  36. [37]Seyrantepe V Hinek A Peng J Fedjaev M Ernest S Kadota Y Enzymatic activity of lysosomal carboxypeptidase (cathepsin) A is required for proper elastic fiber formation and inactivation of endothelin-1 Circulation 2008 Apr 15 117 15 1973 1981 18391110
  37. [38]Dridi L Seyrantepe V Fougerat A Pan X Bonneil E Thibault P Positive regulation of insulin signaling by neuraminidase 1 Diabetes 2013 7 62 7 2338 2346 23520133 PMC3712076 ** The results described in this paper propose Neu1 as a novel component of the signaling pathways of energy metabolism and glucose uptake.
  38. [39]Yogalingam G Bonten EJ van de Vlekkert D Hu H Moshiach S Connell SA Neuraminidase 1 is a negative regulator of lysosomal exocytosis Dev Cell 2008 7 15 1 74 86 18606142 PMC2664108 ** This paper uncovers the role of NEU1 in regulating lysosomal exocytosis and links exacerbation of this process to the pathogenesis of sialidosis.
  39. [40]Griffiths GM Tsun A Stinchcombe JC The immunological synapse: a focal point for endocytosis and exocytosis The Journal of cell biology 2010 May 3 189 3 399 406 20439993 PMC2867296
  40. [41]Samie MA Xu H Lysosomal exocytosis and lipid storage disorders Journal of lipid research 2014 Mar 25 55 6 995 1009 24668941 PMC4031951
  41. [42]Rodriguez A Webster P Ortego J Andrews NW Lysosomes behave as Ca2+-regulated exocytic vesicles in fibroblasts and epithelial cells The Journal of cell biology 1997 Apr 7 137 1 93 104 9105039 PMC2139854
  42. [43]Jaiswal JK Andrews NW Simon SM Membrane proximal lysosomes are the major vesicles responsible for calcium-dependent exocytosis in nonsecretory cells The Journal of cell biology 2002 Nov 25 159 4 625 635 12438417 PMC2173094
  43. [44]Stinchcombe J Bossi G Griffiths GM Linking albinism and immunity: the secrets of secretory lysosomes Science 2004 Jul 2 305 5680 55 59 15232098
  44. [45]Luzio JP Hackmann Y Dieckmann NM Griffiths GM The biogenesis of lysosomes and lysosome-related organelles Cold Spring Harbor perspectives in biology 2014 9 6 9 a016840 25183830 PMC4142962
  45. [46]Holt OJ Gallo F Griffiths GM Regulating secretory lysosomes Journal of biochemistry 2006 7 140 1 7 12 16877763
  46. [47]Schwake M Schroder B Saftig P Lysosomal membrane proteins and their central role in physiology Traffic 2013 7 14 7 739 748 23387372
  47. [48]Kima PE Burleigh B Andrews NW Surface-targeted lysosomal membrane glycoprotein-1 (Lamp-1) enhances lysosome exocytosis and cell invasion by Trypanosoma cruzi Cellular microbiology 2000 12 2 6 477 486 11207602
  48. [49]Wu X Steigelman KA Bonten E Hu H He W Ren T Vacuolization and alterations of lysosomal membrane proteins in cochlear marginal cells contribute to hearing loss in neuraminidase 1-deficient mice Biochim Biophys Acta 2010 2 1802 2 259 268 19857571 PMC2818351
  49. [50]d’Azzo A Kolodny EH Bonten E Annunziata I Storage disease of the reticuloendothelial system 2009 7th edition ed. New York Nathan and Oski’s
  50. [51]Bellettato CM Scarpa M Pathophysiology of neuropathic lysosomal storage disorders Journal of inherited metabolic disease 2010 8 33 4 347 362 20429032
  51. [52]Sidransky E Lopez G The link between the GBA gene and parkinsonism The Lancet Neurology 2012 11 11 11 986 998 23079555 PMC4141416
  52. [53]Keilani S Lun Y Stevens AC Williams HN Sjoberg ER Khanna R Lysosomal dysfunction in a mouse model of Sandhoff disease leads to accumulation of ganglioside-bound amyloid-beta peptide The Journal of neuroscience: the official journal of the Society for Neuroscience 2012 4 11 32 15 5223 5236 22496568 PMC6622109
  53. [54]Martins C Hulkova H Dridi L Dormoy-Raclet V Grigoryeva L Choi Y Neuroinflammation, mitochondrial defects and neurodegeneration in mucopolysaccharidosis III type C mouse model Brain: a journal of neurology 2015 2 138 Pt 2 336 355 25567323 PMC4306821
  54. [55]Ohmi K Zhao HZ Neufeld EF Defects in the medial entorhinal cortex and dentate gyrus in the mouse model of Sanfilippo syndrome type B PloS one 2011 6 11 e27461 22096577 PMC3212581
  55. [56]Ohmi K Kudo LC Ryazantsev S Zhao HZ Karsten SL Neufeld EF Sanfilippo syndrome type B, a lysosomal storage disease, is also a tauopathy Proceedings of the National Academy of Sciences of the United States of America 2009 May 19 106 20 8332 8337 19416848 PMC2677546
  56. [57]Seyrantepe V Iannello A Liang F Kanshin E Jayanth P Samarani S Regulation of phagocytosis in macrophages by neuraminidase 1 J Biol Chem 2010 Jan 1 285 1 206 215 19889639 PMC2804167
  57. [58]Ortolano S Vieitez I Navarro C Spuch C Treatment of lysosomal storage diseases: recent patents and future strategies Recent patents on endocrine, metabolic & immune drug discovery 2014 1 8 1 9 25 24433521
  58. [59]Bonten EJ Wang D Toy JN Mann L Mignardot A Yogalingam G Targeting macrophages with baculovirus-produced lysosomal enzymes: implications for enzyme replacement therapy of the glycoprotein storage disorder galactosialidosis FASEB J 2004 In Press. 15084520
  59. [60]Wang D Bonten EJ Yogalingam G Mann L d'Azzo A Short-term, high dose enzyme replacement therapy in sialidosis mice Molecular genetics and metabolism 2005 7 85 3 181 189 15979029
  60. [61]Bonten EJ d'Azzo A Lysosomal neuraminidase Catalytic activation in insect cells is controlled by the protective protein/cathepsin A J Biol Chem 2000 275 48 37657 37663 10982818
  61. [62]Hu H Gomero E Bonten E Gray JT Allay J Wu Y Preclinical dose-finding study with a liver-tropic, recombinant AAV-2/8 vector in the mouse model of galactosialidosis Molecular therapy: the journal of the American Society of Gene Therapy 2012 2 20 2 267 274 22008912 PMC3277225 ** This paper reports the first preclinical studies for the treatment of Galactosialidosis using an in-vivo gene therapy approach.
  62. [63]Pattison S Pankarican M Rupar CA Graham FL Igdoura SA Five novel mutations in the lysosomal sialidase gene (NEU1) in type II sialidosis patients and assessment of their impact on enzyme activity and intracellular targeting using adenovirus-mediated expression Hum Mutat 2004 1 23 1 32 39 14695530
  63. [64]Sergi C Penzel R Uhl J Zoubaa S Dietrich H Decker N Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene Human genetics 2001 10 109 4 421 428 11702224
  64. [65]Huang YZ Lai SC Lu CS Weng YH Chuang WL Chen RS Abnormal cortical excitability with preserved brainstem and spinal reflexes in sialidosis type I Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 2008 5 119 5 1042 1050 18343720
  65. [66]Seyrantepe V Poupetova H Froissart R Zabot MT Maire I Pshezhetsky AV Molecular pathology of NEU1 gene in sialidosis Hum Mutat 2003 22 5 343 352 14517945
  66. [67]Sekijima Y Nakamura K Kishida D Narita A Adachi K Ohno K Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene Internal medicine 2013 52 1 119 124 23291686
  67. [68]Naganawa Y Itoh K Shimmoto M Takiguchi K Doi H Nishizawa Y Molecular and structural studies of Japanese patients with sialidosis type 1 Journal of human genetics 2000 45 4 241 249 10944856

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Authors
D’Azzo, A., Machado, E., & Annunziata, I.
Affiliations
St. Jude Children's Research Hospital (US)
ORCID
Venue
Expert Opinion on Orphan Drugs
Publisher
Informa Healthcare
Published
2015-04-13
Volume
3
Issue
5
Pages
491-504
ISSN
2167-8707 (ISSN-L)
DOI
10.1517/21678707.2015.1025746
PMC
PMC4777310
OpenAlex
W2075095334
Cited by
76
References
1
Citations by year
2026: 9 · 2025: 4 · 2024: 8 · 2023: 4 · 2022: 9 · 2021: 8 · 2020: 9 · 2019: 9 · 2018: 9 · 2017: 6 · 2012: 1
FWCI
3.34
Type
journal article
Language
en
Open access
Locations
  • Expert Opinion on Orphan Drugs (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Georgia Clinical and Translational Science Alliance
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM104981, R01GM060950)
  • National Institute of Diabetes and Digestive and Kidney Diseases (Z01DK052025, R01DK052025, R01DK095169)
Topics
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
Keywords
sialidosis, NEU1, lysosomal storage disease, cathepsin A, pathogenesis, therapeutic target, galactosialidosis, clinical trials, rare diseases

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