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image of Role and Mechanisms Underlying NEU1 in Alzheimer's Disease: A 
Pathogenetic and Therapeutic Perspective

Abstract

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by a loss of cognitive function, behavioral changes, and neurodegeneration. The occurrence of Aβ plaques in the brain and the formation of neurofibrillary tangles (NFTs) are hallmarks of the disease. Neuroinflammation and glycoprotein metabolism, particularly neuraminidase 1 (NEU1), are emerging as crucial factors in AD pathogenesis and remain underexplored. This review aims to identify the role of NEU1 in AD pathogenesis and its potential as a therapeutic target. Studies published between 2017 and 2024 were included, focusing on AD, dementia, pathology, the amyloid hypothesis, treatment, neuraminidase, and neuraminidase modulators using PubMed, Google Scholar, Scopus, EMBASE, and other databases. To address the underlying pathophysiology of AD, several therapeutic strategies target key proteins and enzymes involved in Aβ and tau aggregation, as well as neurotransmitter signalling. Inhibitors of cholinesterase are currently approved for symptomatic treatment. However, these medications only provide modest relief and do not modify disease progression. Emerging evidence demonstrated that NEU1 deficiency leads to the accumulation of amyloid precursor protein (APP) and Aβ precursor. This accumulation disrupts lysosomal function and autophagy, exacerbating Aβ and tau pathology. Modulating NEU1 activity by developing specific activators offers a promising therapeutic approach for AD. Such compounds could reduce Aβ production, enhance Aβ clearance, and alleviate neuroinflammation. In conclusion, targeting NEU1 represents a promising avenue for AD therapies. Further study is necessary to elucidate the precise mechanisms for NEU1's contribution to AD and to elucidate effective NEU1-based interventions.

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2026-04-03
2026-04-17

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References

  1. Maurer K. Volk S. Gerbaldo H. Auguste D and Alzheimer’s disease. Lancet 1997 349 9064 1546 1549 10.1016/S0140‑6736(96)10203‑8 9167474
    [Google Scholar]
  2. 2018 Alzheimer’s disease facts and figures. Alzheimers Dement. 2018 14 3 367 429 10.1016/j.jalz.2018.02.001
    [Google Scholar]
  3. Zvěřová M. Clinical aspects of Alzheimer’s disease. Clin. Biochem. 2019 72 3 6 10.1016/j.clinbiochem.2019.04.015 31034802
    [Google Scholar]
  4. Gonzales M.M. Garbarino V.R. Pollet E. Palavicini J.P. Kellogg D.L. Kraig E. Orr M.E. Biological aging processes underlying cognitive decline and neurodegenerative disease. J. Clin. Invest. 2022 132 10 158453 10.1172/JCI158453 35575089
    [Google Scholar]
  5. Moloney C.M. Lowe V.J. Murray M.E. Visualization of neurofibrillary tangle maturity in Alzheimer’s disease: A clinicopathologic perspective for biomarker research. Alzheimers Dement. 2021 17 9 1554 1574 10.1002/alz.12321 33797838
    [Google Scholar]
  6. Walker L.C. Aβ Plaques. Free Neuropathol. 2020 1 31 10.17879/freeneuropathology‑2020‑3025 33345256
    [Google Scholar]
  7. Magalingam K.B. Radhakrishnan A. Ping N.S. Haleagrahara N. Current concepts of neurodegenerative mechanisms in Alzheimer’s disease. BioMed Res. Int. 2018 2018 1 1 12 10.1155/2018/3740461 29707568
    [Google Scholar]
  8. Sharma C. Kim S.R. Oxidative stress: Culprit or consequence in Alzheimer’s amyloidopathy. Neura.l Regen. Res. 2023 18 9 1948 1949 10.4103/1673‑5374.367843 36926715
    [Google Scholar]
  9. Chávez-Gutiérrez L. Szaruga M. Mechanisms of neurodegeneration - Insights from familial Alzheimer’s disease. Semin. Cell Dev. Biol. 2020 105 75 85 10.1016/j.semcdb.2020.03.005 32418657
    [Google Scholar]
  10. Lane C.A. Hardy J. Schott J.M. Alzheimer’s disease. Eur. J. Neurol. 2018 25 1 59 70 10.1111/ene.13439 28872215
    [Google Scholar]
  11. Bereczki E. Branca R.M. Francis P.T. Pereira J.B. Baek J.H. Hortobágyi T. Winblad B. Ballard C. Lehtiö J. Aarsland D. Synaptic markers of cognitive decline in neurodegenerative diseases: A proteomic approach. Brain 2018 141 2 582 595 10.1093/brain/awx352 29324989
    [Google Scholar]
  12. von Gunten A. Nogueira E. Parmentier H. Gomes I. Neurocognitive disorders in old age: Alzheimer’s disease, frontotemporal dementia, dementia with Lewy bodies, and prion and infectious diseases. Primary Care Mental Health, in Older People. Cham Springer 2019 251 298 10.1007/978‑3‑030‑10814‑4_21
    [Google Scholar]
  13. John A. Reddy P.H. Synaptic basis of Alzheimer’s disease: Focus on synaptic amyloid beta, P-tau and mitochondria. Ageing Res. Rev. 2021 65 101208 10.1016/j.arr.2020.101208 33157321
    [Google Scholar]
  14. Breijyeh Z. Karaman R. Comprehensive review on Alzheimer’s disease: Causes and treatment. Molecules 2020 25 24 5789 10.3390/molecules25245789 33302541
    [Google Scholar]
  15. Hase Y. Horsburgh K. Ihara M. Kalaria R.N. White matter degeneration in vascular and other ageing‐related dementias. J. Neurochem. 2018 144 5 617 633 10.1111/jnc.14271 29210074
    [Google Scholar]
  16. Silva M.V.F. Loures C.M.G. Alves L.C.V. de Souza L.C. Borges K.B.G. Carvalho M.G. Alzheimer’s disease: Risk factors and potentially protective measures. J. Biomed. Sci. 2019 26 1 33 10.1186/s12929‑019‑0524‑y
    [Google Scholar]
  17. Liu P.P. Xie Y. Meng X.Y. Kang J.S. History and progress of hypotheses and clinical trials for Alzheimer’s disease. Signal Transduct. Target. Ther. 2019 4 1 29 10.1038/s41392‑019‑0063‑8 31637009
    [Google Scholar]
  18. Chen X.Q. Mobley W.C. Exploring the pathogenesis of Alzheimer disease in basal forebrain cholinergic neurons: Converging insights from alternative hypotheses. Front. Neurosci. 2019 13 446 10.3389/fnins.2019.00446 31133787
    [Google Scholar]
  19. Hampel H. Mesulam M.M. Cuello A.C. Farlow M.R. Giacobini E. Grossberg G.T. Khachaturian A.S. Vergallo A. Cavedo E. Snyder P.J. Khachaturian Z.S. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain 2018 141 7 1917 1933 10.1093/brain/awy132 29850777
    [Google Scholar]
  20. Bukke V.N. Villani R. Archana M. Wawrzyniak A. Balawender K. Orkisz S. Ferraro L. Serviddio G. Cassano T. The glucose metabolic pathway as a potential target for therapeutics: Crucial role of glycosylation in Alzheimer’s disease. Int. J. Mol. Sci. 2020 21 20 7739 10.3390/ijms21207739 33086751
    [Google Scholar]
  21. Zhao J. Lang M. New insight into protein glycosylation in the development of Alzheimer’s disease. Cell Death Discov. 2023 9 1 314 10.1038/s41420‑023‑01617‑5 37626031
    [Google Scholar]
  22. Reichert J.S. SV2A-just a synaptic vesicle protein? Unravelling the interaction of SV2A and mitochondria in the pathogenesis and therapy of Morbus Alzheimer. Dissertation, Mainz, Johannes Gutenberg- Universität Mainz 2022
    [Google Scholar]
  23. Hadi F. Akrami H. Shahpasand K. Fattahi M.R. Wnt signalling pathway and tau phosphorylation: A comprehensive study on known connections. Cell Biochem. Funct. 2020 38 6 686 694 10.1002/cbf.3530 32232872
    [Google Scholar]
  24. Kianpour Rad S. Arya A. Karimian H. Madhavan P. Rizwan F. Koshy S. Prabhu G. Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: Link between type 2 diabetes and Alzheimer’s disease. Drug Des. Devel. Ther. 2018 12 3999 4021 10.2147/DDDT.S173970 30538427
    [Google Scholar]
  25. Keil J.M. Rafn G.R. Turan I.M. Aljohani M.A. Sahebjam-Atabaki R. Sun X.L. Sialidase inhibitors with different mechanisms. J. Med. Chem. 2022 65 20 13574 13593 10.1021/acs.jmedchem.2c01258 36252951
    [Google Scholar]
  26. Abdulridha M.K. Al-Marzoqi A.H. Al-awsi G.R.L. Mubarak S.M.H. Heidarifard M. Ghasemian A. Anticancer effects of herbal medicine compounds and novel formulations: A literature review. J. Gastrointest. Cancer 2020 51 3 765 773 10.1007/s12029‑020‑00385‑0 32140897
    [Google Scholar]
  27. Khan A. Sergi C.M. NEU1—A unique therapeutic target for Alzheimer’s disease. Front. Pharmacol. 2022 13 902259 10.3389/fphar.2022.902259 35847014
    [Google Scholar]
  28. Settembre C. Perera R.M. Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology. Nat. Rev. Mol. Cell Biol. 2024 25 3 223 245 10.1038/s41580‑023‑00676‑x 38001393
    [Google Scholar]
  29. Ballabio A. Bonifacino J.S. Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat. Rev. Mol. Cell Biol. 2020 21 2 101 118 10.1038/s41580‑019‑0185‑4 31768005
    [Google Scholar]
  30. Zhang W. Xu C. Sun J. Shen H.M. Wang J. Yang C. Impairment of the autophagy–lysosomal pathway in Alzheimer’s diseases: Pathogenic mechanisms and therapeutic potential. Acta Pharm. Sin. B 2022 12 3 1019 1040 10.1016/j.apsb.2022.01.008 35530153
    [Google Scholar]
  31. Allendorf D.H. Brown G.C. Neu1 is released from activated microglia, stimulating microglial phagocytosis and sensitizing neurons to glutamate. Front. Cell. Neurosci. 2022 16 917884 10.3389/fncel.2022.917884 35693885
    [Google Scholar]
  32. Aljohani M.A. Sasaki H. Sun X.L. Cellular translocation and secretion of sialidases. J. Biol. Chem. 2024 300 9 107671 10.1016/j.jbc.2024.107671 39128726
    [Google Scholar]
  33. Du J. Shui H. Chen R. Dong Y. Xiao C. Hu Y. Wong N.K. Neuraminidase-1 (NEU1): Biological roles and therapeutic relevance in human disease. Curr. Issues Mol. Biol. 2024 46 8 8031 8052 10.3390/cimb46080475 39194692
    [Google Scholar]
  34. Khan A. Das S. Sergi C. Therapeutic potential of Neu1 in Alzheimer’s disease via the immune system. Am. J. Alzheimers Dis. Other Demen. 2021 36 1533317521996147 10.1177/1533317521996147 33719595
    [Google Scholar]
  35. Rawal P. Zhao L. Sialometabolism in brain health and Alzheimer’s disease. Front. Neurosci. 2021 15 648617 10.3389/fnins.2021.648617 33867926
    [Google Scholar]
  36. Pshezhetsky A.V. Ashmarina M. Keeping it trim: Roles of neuraminidases in CNS function. Glycoconj. J. 2018 35 4 375 386 10.1007/s10719‑018‑9837‑4 30088207
    [Google Scholar]
  37. Timur Z.K. Inci O.K. Demir S.A. Seyrantepe V. Sialidase neu4 deficiency is associated with neuroinflammation in mice. Glycoconj. J. 2021 38 6 649 667 10.1007/s10719‑021‑10017‑9 34686927
    [Google Scholar]
  38. Khan A. Sergi C. Sialidosis: A review of morphology and molecular biology of a rare pediatric disorder. Diagnostics 2018 8 2 29 10.3390/diagnostics8020029 29693572
    [Google Scholar]
  39. Liao H. Klaus C. Neumann H. Control of innate immunity by sialic acids in the nervous tissue. Int. J. Mol. Sci. 2020 21 15 5494 10.3390/ijms21155494 32752058
    [Google Scholar]
  40. Fremuth L.E. Immunomodulatory Roles of the Lysosomal Sialidase Neuraminidase 1. The University of Tennessee Health Science Center 2022
    [Google Scholar]
  41. Li Y. Liu Y. Wang R. Ao R. Xiang F. Zhang X. Wang X. Yu S. Clinical and structural characteristics of NEU1 variants causing sialidosis type 1. J. Mov. Disord. 2024 17 3 282 293 10.14802/jmd.23145 38600684
    [Google Scholar]
  42. Allendorf D. Role of neuraminidase-mediated desialylation in microglial activation. Apollo - University of Cambridge Repository 2021
    [Google Scholar]
  43. Knopman D.S. Amieva H. Petersen R.C. Chételat G. Holtzman D.M. Hyman B.T. Nixon R.A. Jones D.T. Alzheimer disease. Nat. Rev. Dis. Primers 2021 7 1 33 10.1038/s41572‑021‑00269‑y 33986301
    [Google Scholar]
  44. Cao J. Zhong M.B. Toro C.A. Zhang L. Cai D. Endo-lysosomal pathway and ubiquitin-proteasome system dysfunction in Alzheimer’s disease pathogenesis. Neurosci. Lett. 2019 703 68 78 10.1016/j.neulet.2019.03.016 30890471
    [Google Scholar]
  45. Nixon R.A. Amyloid precursor protein and endosomal‐lysosomal dysfunction in Alzheimer’s disease: Inseparable partners in a multifactorial disease. FASEB J. 2017 31 7 2729 2743 10.1096/fj.201700359 28663518
    [Google Scholar]
  46. Chai A.B. Leung G.K.F. Callaghan R. Gelissen I.C. P‐glycoprotein: A role in the export of amyloid‐β in Alzheimer’s disease? FEBS J. 2020 287 4 612 625 10.1111/febs.15148 31750987
    [Google Scholar]
  47. Bruni A.C. Bernardi L. Gabelli C. From beta amyloid to altered proteostasis in Alzheimer’s disease. Ageing Res. Rev. 2020 64 101126 10.1016/j.arr.2020.101126 32683041
    [Google Scholar]
  48. Wang L. Mao X. Role of retinal amyloid-β in neurodegenerative diseases: Overlapping mechanisms and emerging clinical applications. Int. J. Mol. Sci. 2021 22 5 2360 10.3390/ijms22052360 33653000
    [Google Scholar]
  49. Smith M.A. Rottkamp C.A. Nunomura A. Raina A.K. Perry G. Oxidative stress in Alzheimer’s disease. Biochim. Biophys. Acta Mol. Basis Dis. 2000 1502 1 139 144 10.1016/S0925‑4439(00)00040‑5
    [Google Scholar]
  50. Martemucci G. Costagliola C. Mariano M. D’andrea L. Napolitano P. D’Alessandro A.G. Free radical properties, source and targets, antioxidant consumption and health. Oxygen 2022 2 2 48 78 10.3390/oxygen2020006
    [Google Scholar]
  51. Aranda-Rivera A.K. Cruz-Gregorio A. Arancibia-Hernández Y.L. Hernández-Cruz E.Y. Pedraza-Chaverri J. RONS and oxidative stress: An overview of basic concepts. Oxygen 2022 2 4 437 478 10.3390/oxygen2040030
    [Google Scholar]
  52. Valko M. Leibfritz D. Moncol J. Cronin M.T.D. Mazur M. Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 2007 39 1 44 84 10.1016/j.biocel.2006.07.001 16978905
    [Google Scholar]
  53. Bedard K. Krause K.H. The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology. Physiol. Rev. 2007 87 1 245 313 10.1152/physrev.00044.2005 17237347
    [Google Scholar]
  54. Dröge W. Free radicals in the physiological control of cell function. Physiol. Rev. 2002 82 1 47 95 10.1152/physrev.00018.2001 11773609
    [Google Scholar]
  55. Juan C.A. Pérez de la Lastra J.M. Plou F.J. Pérez-Lebeña E. The chemistry of reactive oxygen species (ROS) revisited: Outlining their role in biological macromolecules (DNA, Lipids and Proteins) and induced pathologies. Int. J. Mol. Sci. 2021 22 9 4642 10.3390/ijms22094642 33924958
    [Google Scholar]
  56. Bisht K. Sharma K. Tremblay M.È. Chronic stress as a risk factor for Alzheimer’s disease: Roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress. Neurobiol. Stress 2018 9 9 21 10.1016/j.ynstr.2018.05.003 29992181
    [Google Scholar]
  57. Psefteli P.M. Kitscha P. Vizcay G. Fleck R. Chapple S.J. Mann G.E. Fowler M. Siow R.C. Glycocalyx sialic acids regulate Nrf2-mediated signaling by fluid shear stress in human endothelial cells. Redox Biol. 2021 38 101816 10.1016/j.redox.2020.101816 33340902
    [Google Scholar]
  58. Guo Z. Tuo H. Tang N. Liu F.Y. Ma S.Q. An P. Yang D. Wang M.Y. Fan D. Yang Z. Tang Q.Z. Neuraminidase 1 deficiency attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory via AMPK-SIRT3 pathway in diabetic cardiomyopathy mice. Int. J. Biol. Sci. 2022 18 2 826 840 10.7150/ijbs.65938 35002528
    [Google Scholar]
  59. Heimerl M. Gausepohl T. Mueller J.H. Ricke-Hoch M. Neuraminidases—Key players in the inflammatory response after pathophysiological cardiac stress and potential new therapeutic targets in cardiac disease. Biology 2022 11 8 1229 10.3390/biology11081229 36009856
    [Google Scholar]
  60. Sackmann V. Ansell A. Sackmann C. Lund H. Harris R.A. Hallbeck M. Nilsberth C. Anti-inflammatory (M2) macrophage media reduce transmission of oligomeric amyloid beta in differentiated SH-SY5Y cells. Neurobiol. Aging 2017 60 173 182 10.1016/j.neurobiolaging.2017.08.022 28969867
    [Google Scholar]
  61. Hemonnot A.L. Hua J. Ulmann L. Hirbec H. Microglia in Alzheimer disease: Well-known targets and new opportunities. Front. Aging Neurosci. 2019 11 233 10.3389/fnagi.2019.00233 31543810
    [Google Scholar]
  62. Annunziata I. Patterson A. Helton D. Hu H. Moshiach S. Gomero E. Nixon R. d’Azzo A. Lysosomal NEU1 deficiency affects amyloid precursor protein levels and amyloid-β secretion via deregulated lysosomal exocytosis. Nat. Commun. 2013 4 1 2734 10.1038/ncomms3734 24225533
    [Google Scholar]
  63. Jorfi M. Maaser-Hecker A. Tanzi R.E. The neuroimmune axis of Alzheimer’s disease. Genome Med. 2023 15 1 6 10.1186/s13073‑023‑01155‑w 36703235
    [Google Scholar]
  64. Chen X. Holtzman D.M. Emerging roles of innate and adaptive immunity in Alzheimer’s disease. Immunity 2022 55 12 2236 2254 10.1016/j.immuni.2022.10.016 36351425
    [Google Scholar]
  65. Le Page A. Dupuis G. Frost E.H. Larbi A. Pawelec G. Witkowski J.M. Fulop T. Role of the peripheral innate immune system in the development of Alzheimer’s disease. Exp. Gerontol. 2018 107 59 66 10.1016/j.exger.2017.12.019 29275160
    [Google Scholar]
  66. Kawecki C. Bocquet O. Schmelzer C.E.H. Heinz A. Ihling C. Wahart A. Romier B. Bennasroune A. Blaise S. Terryn C. Linton K.J. Martiny L. Duca L. Maurice P. Identification of CD36 as a new interaction partner of membrane NEU1: Potential implication in the pro-atherogenic effects of the elastin receptor complex. Cell. Mol. Life Sci. 2019 76 4 791 807 10.1007/s00018‑018‑2978‑6 30498996
    [Google Scholar]
  67. Fremuth L.E. Hu H. van de Vlekkert D. Annunziata I. Weesner J.A. Gomero E. Neuraminidase 1 regulates the cellular state of microglia by modulating the sialylation of Trem2. bioRxiv 2024 2024.05
    [Google Scholar]
  68. Lillehoj E.P. Luzina I.G. Atamas S.P. Mammalian neuraminidases in immune-mediated diseases: Mucins and beyond. Front. Immunol. 2022 13 883079 10.3389/fimmu.2022.883079 35479093
    [Google Scholar]
  69. Maestú F. de Haan W. Busche M.A. DeFelipe J. Neuronal excitation/inhibition imbalance: Core element of a translational perspective on Alzheimer pathophysiology. Ageing Res. Rev. 2021 69 101372 10.1016/j.arr.2021.101372 34029743
    [Google Scholar]
  70. Targa D.A.H. Matosin N. Ooi L. Neuronal hyperexcitability in Alzheimer’s disease: What are the drivers behind this aberrant phenotype? Transl. Psychiatry 2022 12 1 257 10.1038/s41398‑022‑02024‑7 35732622
    [Google Scholar]
  71. Miyazaki T. Abe H. Uchida H. Takahashi T. Translational medicine of the glutamate AMPA receptor. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. 2021 97 1 1 21 10.2183/pjab.97.001 33431723
    [Google Scholar]
  72. Lisek M. Zylinska L. Boczek T. Ketamine and calcium signaling—A crosstalk for neuronal physiology and pathology. Int. J. Mol. Sci. 2020 21 21 8410 10.3390/ijms21218410 33182497
    [Google Scholar]
  73. Oh M. Ha D.I. Son C. Kang J.G. Hwang H. Moon S.B. Kim M. Nam J. Kim J.S. Song S.Y. Kim Y.S. Park S. Yoo J.S. Ko J.H. Park K. Defect in cytosolic Neu2 sialidase abrogates lipid metabolism and impairs muscle function in vivo. Sci. Rep. 2022 12 1 3216 10.1038/s41598‑022‑07033‑6 35217678
    [Google Scholar]
  74. Abe C. Yi Y. Hane M. Kitajima K. Sato C. Acute stress-induced change in polysialic acid levels mediated by sialidase in mouse brain. Sci. Rep. 2019 9 1 9950 10.1038/s41598‑019‑46240‑6 31289315
    [Google Scholar]
  75. Pan X. De Britto Pará De Aragão C. Velasco-Martin J.P. Priestman D.A. Wu H.Y. Takahashi K. Yamaguchi K. Sturiale L. Garozzo D. Platt F.M. Lamarche-Vane N. Morales C.R. Miyagi T. Pshezhetsky A.V. Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides. FASEB J. 2017 31 8 3467 3483 10.1096/fj.201601299R 28442549
    [Google Scholar]
  76. Guo L. Tian J. Du H. Mitochondrial dysfunction and synaptic transmission failure in Alzheimer’s disease. J. Alzheimers Dis. 2017 57 4 1071 1086 10.3233/JAD‑160702 27662318
    [Google Scholar]
  77. Warpechowski M. Warpechowski J. Kulczyńska-Przybik A. Mroczko B. Biomarkers of activity-dependent plasticity and persistent enhancement of synaptic transmission in Alzheimer disease: A review of the current status. Med. Sci. Monit. 2023 29 938826 10.12659/MSM.938826 36600577
    [Google Scholar]
  78. Kashyap G. Bapat D. Das D. Gowaikar R. Amritkar R.E. Rangarajan G. Ravindranath V. Ambika G. Synapse loss and progress of Alzheimer’s disease -A network model. Sci. Rep. 2019 9 1 6555 10.1038/s41598‑019‑43076‑y 31024073
    [Google Scholar]
  79. Marcello E. Di Luca M. Gardoni F. Synapse-to-nucleus communication: From developmental disorders to Alzheimer’s disease. Curr. Opin. Neurobiol. 2018 48 160 166 10.1016/j.conb.2017.12.017 29316492
    [Google Scholar]
  80. Dolphin A.C. Lee A. Presynaptic calcium channels: Specialized control of synaptic neurotransmitter release. Nat. Rev. Neurosci. 2020 21 4 213 229 10.1038/s41583‑020‑0278‑2 32161339
    [Google Scholar]
  81. Heilman K.M. Nadeau S.E. Emotional and neuropsychiatric disorders associated with Alzheimer’s disease. Neurotherapeutics 2022 19 1 99 116 10.1007/s13311‑021‑01172‑w 35013934
    [Google Scholar]
  82. Mendez M.F. Degenerative dementias: Alterations of emotions and mood disorders. Handb. Clin. Neurol. 2021 183 261 281 10.1016/B978‑0‑12‑822290‑4.00012‑8 34389121
    [Google Scholar]
  83. Ikeda A. Komamizu M. Hayashi A. Yamasaki C. Okada K. Kawabe M. Komatsu M. Shiozaki K. Neu1 deficiency induces abnormal emotional behavior in zebrafish. Sci. Rep. 2021 11 1 13477 10.1038/s41598‑021‑92778‑9 34188220
    [Google Scholar]
  84. Okada K. Takase R. Hamaoka Y. Honda A. Ikeda A. Hokazono Y. Maeda Y. Hayasaka O. Kotani T. Komatsu M. Shiozaki K. Establishment and characterization of Neu1-knockout zebrafish and its abnormal clinical phenotypes. Biochem. J. 2020 477 15 2841 2857 10.1042/BCJ20200348 32686823
    [Google Scholar]
  85. Abdullahi M. Uzairu A. Shallangwa G.A. Mamza P.A. Ibrahim M.T. Ahmad I. Patel H. Structure-based drug design, molecular dynamics simulation, ADMET, and quantum chemical studies of some thiazolinones targeting influenza neuraminidase. J. Biomol. Struct. Dyn. 2023 41 23 13829 13843 10.1080/07391102.2023.2208225 37158006
    [Google Scholar]
  86. Zhu W. Zhou Y. Guo L. Feng S. Biological function of sialic acid and sialylation in human health and disease. Cell Death Discov. 2024 10 1 415 10.1038/s41420‑024‑02180‑3 39349440
    [Google Scholar]
  87. Fastenau C. Solano L. Wickline J.L. Smith S. Odfalk K.F. Bieniek K.F. Hopp S.C. Increased Sialylation in Alzheimer’s Disease Models. Alzheimers Dement. 2022 18 S4 069304 10.1002/alz.069304
    [Google Scholar]
  88. Tabakacılar D. Investigation of the biological role of mouse acylneuraminyl hydrolase enzymes in the regulation of neuroinflammation. Izmir Institute of Technology 2022
    [Google Scholar]
  89. Karmakar J. Roy S. Mandal C. Modulation of TLR4 sialylation mediated by a sialidase Neu1 and impairment of its signaling in Leishmania donovani infected macrophages. Front. Immunol. 2019 10 2360 10.3389/fimmu.2019.02360 31649671
    [Google Scholar]
  90. Mosca R. van de Vlekkert D. Campos Y. Fremuth L.E. Cadaoas J. Koppaka V. Kakkis E. Tifft C. Toro C. Allievi S. Gellera C. Canafoglia L. Visser G. Annunziata I. d’Azzo A. Conventional and unconventional therapeutic strategies for sialidosis type I. J. Clin. Med. 2020 9 3 695 10.3390/jcm9030695 32143456
    [Google Scholar]
  91. Zeng H. Xu L. Zou Y. Wang S. Romidepsin and metformin nanomaterials delivery on streptozocin for the treatment of Alzheimer’s disease in animal model. Biomed. Pharmacother. 2021 141 111864 10.1016/j.biopha.2021.111864 34323698
    [Google Scholar]
  92. Alipourfard F. Shajiee H. Nazari-Serenjeh F. Hojati V. Alirezaie M. Betaine attenuates oxidative stress and cognitive dysfunction in an amyloid β-induced rat model of Alzheimer’s disease. Res. Pharm. Sci. 2023 18 3 270 278 10.4103/1735‑5362.371583 37593165
    [Google Scholar]
  93. Hunter C. Influence of diversity in sialic acid presentation on human neuraminidase enzyme activity. Doctoral. University of Alberta 2020
    [Google Scholar]
  94. Demina E.P. Smutova V. Pan X. Fougerat A. Guo T. Zou C. Chakraberty R. Snarr B.D. Shiao T.C. Roy R. Orekhov A.N. Miyagi T. Laffargue M. Sheppard D.C. Cairo C.W. Pshezhetsky A.V. Neuraminidases 1 and 3 trigger atherosclerosis by desialylating low‐density lipoproteins and increasing their uptake by macrophages. J. Am. Heart Assoc. 2021 10 4 018756 10.1161/JAHA.120.018756 33554615
    [Google Scholar]
  95. Glanz V.Y. Myasoedova V.A. Grechko A.V. Orekhov A.N. Sialidase activity in human pathologies. Eur. J. Pharmacol. 2019 842 345 350 10.1016/j.ejphar.2018.11.014 30439363
    [Google Scholar]
  96. Miyagi T. Yamamoto K. Sialidase NEU3 and its pathological significance. Glycoconj. J. 2022 39 5 677 683 10.1007/s10719‑022‑10067‑7 35675020
    [Google Scholar]
  97. Rogers G.W. The development of sialidase inhibitors using structure-based drug design. In: Thesis, PhD Doctor of Philosophy 2017
    [Google Scholar]
  98. Mtambo S.E. Amoako D.G. Somboro A.M. Agoni C. Lawal M.M. Gumede N.S. Khan R.B. Kumalo H.M. Influenza viruses: Harnessing the crucial role of the M2 ion-channel and neuraminidase toward inhibitor design. Molecules 2021 26 4 880 10.3390/molecules26040880 33562349
    [Google Scholar]
  99. Campbell A.C. Tanner J.J. Krause K.L. Optimisation of neuraminidase expression for use in drug discovery by using HEK293-6E cells. Viruses 2021 13 10 1893 10.3390/v13101893 34696326
    [Google Scholar]
  100. Albrecht C. Kuznetsov A.S. Appert-Collin A. Dhaideh Z. Callewaert M. Bershatsky Y.V. Urban A.S. Bocharov E.V. Bagnard D. Baud S. Blaise S. Romier-Crouzet B. Efremov R.G. Dauchez M. Duca L. Gueroult M. Maurice P. Bennasroune A. Transmembrane peptides as a new strategy to inhibit neuraminidase-1 activation. Front. Cell Dev. Biol. 2020 8 611121 10.3389/fcell.2020.611121 33392200
    [Google Scholar]
  101. Yu R. Cheng L.P. Li M. Pang W. Discovery of novel neuraminidase inhibitors by structure-based virtual screening, structural optimization, and bioassay. ACS Med. Chem. Lett. 2019 10 12 1667 1673 10.1021/acsmedchemlett.9b00447 31857844
    [Google Scholar]
  102. Ikeda A. Yamasaki C. Kubo Y. Doi Y. Komamizu M. Komatsu M. Shiozaki K. Alteration of the neuronal and glial cell profiles in Neu1-deficient zebrafish. Glycoconj. J. 2022 39 4 499 512 10.1007/s10719‑022‑10074‑8 35877057
    [Google Scholar]
  103. Xu T. Heon-Roberts R. Moore T. Dubot P. Pan X. Guo T. Secondary deficiency of neuraminidase 1 contributes to CNS pathology in neurological mucopolysaccharidoses via hypersialylation of brain glycoproteins. bioRxiv 2024 2024.04
    [Google Scholar]
  104. Atri A. Current and future treatments in Alzheimer’s disease Seminars in neurology. Thieme Medical Publishers 2019
    [Google Scholar]
  105. Fish P.V. Steadman D. Bayle E.D. Whiting P. New approaches for the treatment of Alzheimer’s disease. Bioorg. Med. Chem. Lett. 2019 29 2 125 133 10.1016/j.bmcl.2018.11.034 30501965
    [Google Scholar]
  106. Cummings J.L. Tong G. Ballard C. Treatment combinations for Alzheimer’s disease: Current and future pharmacotherapy options. J. Alzheimers Dis. 2019 67 3 779 794 10.3233/JAD‑180766 30689575
    [Google Scholar]
  107. Pathan A. Limitations of Alzheimer’s Disease medications. Neuropharmac J. 2023 8 11
    [Google Scholar]
  108. Tonda-Turo C. Origlia N. Mattu C. Accorroni A. Chiono V. Current limitations in the treatment of Parkinson’s and Alzheimer’s diseases: State-of-the-art and future perspective of polymeric carriers. Curr. Med. Chem. 2019 25 41 5755 5771 10.2174/0929867325666180221125759 29473493
    [Google Scholar]
  109. Poon C.H. Wang Y. Fung M.L. Zhang C. Lim L.W. Rodent models of amyloid-beta feature of Alzheimer’s disease: Development and potential treatment implications. Aging Dis. 2020 11 5 1235 1259 10.14336/AD.2019.1026 33014535
    [Google Scholar]
  110. Huang L.K. Chao S.P. Hu C.J. Clinical trials of new drugs for Alzheimer disease. J. Biomed. Sci. 2020 27 1 18 10.1186/s12929‑019‑0609‑7 31906949
    [Google Scholar]
  111. Cummings J. Ritter A. Zhong K. Clinical trials for disease-modifying therapies in Alzheimer’s disease: A primer, lessons learned, and a blueprint for the future. J. Alzheimers Dis. 2018 64 s1 S3 S22 10.3233/JAD‑179901 29562511
    [Google Scholar]
  112. Aisen P.S. Cummings J. Doody R. Kramer L. Salloway S. Selkoe D.J. Sims J. Sperling R.A. Vellas B. The future of anti-amyloid trials. J. Prev. Alzheimers Dis. 2020 7 3 146 151 10.14283/jpad.2020.24 32463066
    [Google Scholar]
  113. Fedele E. Anti-amyloid therapies for Alzheimer’s disease and the amyloid cascade hypothesis. Int. J. Mol. Sci. 2023 24 19 14499 10.3390/ijms241914499 37833948
    [Google Scholar]
  114. Haass C. Selkoe D. If amyloid drives Alzheimer disease, why have anti-amyloid therapies not yet slowed cognitive decline? PLoS Biol. 2022 20 7 3001694 10.1371/journal.pbio.3001694 35862308
    [Google Scholar]
  115. Moussa-Pacha N.M. Abdin S.M. Omar H.A. Alniss H. Al-Tel T.H. BACE1 inhibitors: Current status and future directions in treating Alzheimer’s disease. Med. Res. Rev. 2020 40 1 339 384 10.1002/med.21622 31347728
    [Google Scholar]
  116. Antony D. Sheth P. Swenson A. Smoller C. Maguire K. Grossberg G. Recent advances in Alzheimer’s disease therapy: Clinical trials and literature review of novel enzyme inhibitors targeting amyloid precursor protein. Expert Opin. Pharmacother. 2025 26 1 63 73 10.1080/14656566.2024.2438317 39628105
    [Google Scholar]
  117. Mekala S. Nelson G. Li Y.M. Recent developments of small molecule γ-secretase modulators for Alzheimer’s disease. RSC Med. Chem. 2020 11 9 1003 1022 10.1039/D0MD00196A 33479693
    [Google Scholar]
  118. Perneczky R. Jessen F. Grimmer T. Levin J. Flöel A. Peters O. Froelich L. Anti-amyloid antibody therapies in Alzheimer’s disease. Brain 2023 146 3 842 849 10.1093/brain/awad005 36655336
    [Google Scholar]
  119. Shi M. Chu F. Zhu F. Zhu J. Impact of anti-amyloid-β monoclonal antibodies on the pathology and clinical profile of Alzheimer’s disease: A focus on aducanumab and lecanemab. Front. Aging Neurosci. 2022 14 870517 10.3389/fnagi.2022.870517 35493943
    [Google Scholar]
  120. Congdon E.E. Sigurdsson E.M. Tau-targeting therapies for Alzheimer disease. Nat. Rev. Neurol. 2018 14 7 399 415 10.1038/s41582‑018‑0013‑z 29895964
    [Google Scholar]
  121. Congdon E.E. Ji C. Tetlow A.M. Jiang Y. Sigurdsson E.M. Tau-targeting therapies for Alzheimer disease: Current status and future directions. Nat. Rev. Neurol. 2023 19 12 715 736 10.1038/s41582‑023‑00883‑2 37875627
    [Google Scholar]
  122. Suzuki N. Hatta T. Ito M. Kusakabe K. Anti-amyloid-β antibodies and anti-tau therapies for Alzheimer’s disease: Recent advances and perspectives. Chem. Pharm. Bull. 2024 72 7 602 609 10.1248/cpb.c24‑00069 38945936
    [Google Scholar]
  123. Cheng Z. Han T. Yao J. Wang K. Dong X. Yu F. Huang H. Han M. Liao Q. He S. Lyu W. Li Q. Targeting glycogen synthase kinase-3β for Alzheimer’s disease: Recent advances and future Prospects. Eur. J. Med. Chem. 2024 265 116065 10.1016/j.ejmech.2023.116065 38160617
    [Google Scholar]
  124. Hampel H. Lista S. Mango D. Nisticò R. Perry G. Avila J. Hernandez F. Geerts H. Vergallo A. Afshar M. Aguilar L.F. Akman-Anderson L. Arenas J. Avila J. Babiloni C. Baldacci F. Batrla R. Benda N. Black K.L. Bokde A.L.W. Bonuccelli U. Broich K. Cacciola F. Caraci F. Castrillo J. Cavedo E. Ceravolo R. Chiesa P.A. Corvol J-C. Cuello A.C. Cummings J.L. Depypere H. Dubois B. Duggento A. Emanuele E. Escott-Price V. Federoff H. Ferretti M.T. Fiandaca M. Frank R.A. Garaci F. Geerts H. Giorgi F.S. Goetzl E.J. Graziani M. Haberkamp M. Habert M-O. Hampel H. Herholz K. Hernandez F. Kapogiannis D. Karran E. Kiddle S.J. Kim S.H. Koronyo Y. Koronyo-Hamaoui M. Langevin T. Lehéricy S. Lucía A. Lista S. Lorenceau J. Mango D. Mapstone M. Neri C. Nisticó R. O’Bryant S.E. Palermo G. Perry G. Ritchie C. Rossi S. Saidi A. Santarnecchi E. Schneider L.S. Sporns O. Toschi N. Verdooner S.R. Vergallo A. Villain N. Welikovitch L.A. Woodcock J. Younesi E. Lithium as a treatment for Alzheimer’s disease: The systems pharmacology perspective. J. Alzheimers Dis. 2019 69 3 615 629 10.3233/JAD‑190197 31156173
    [Google Scholar]
  125. Seo D-H. Huh Y.H. Yoo H-J. Cho K. Cheong H-K. Kim E-H. Investigating the hidden mechanism underlying the tau interaction by methylene blue. Preprint 2023 10.21203/rs.3.rs‑2935088/v1
    [Google Scholar]
  126. Soliman A. Bakota L. Brandt R. Microtubule-modulating agents in the fight against neurodegeneration: Will it ever work? Curr. Neuropharmacol. 2022 20 4 782 798 10.2174/1570159X19666211201101020 34852744
    [Google Scholar]
  127. Varidaki A. Hong Y. Coffey E.T. Repositioning microtubule stabilizing drugs for brain disorders. Front. Cell. Neurosci. 2018 12 226 10.3389/fncel.2018.00226 30135644
    [Google Scholar]
  128. Zhang J. Zhang Y. Wang J. Xia Y. Zhang J. Chen L. Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies. Signal Transduct. Target. Ther. 2024 9 1 211 10.1038/s41392‑024‑01911‑3 39174535
    [Google Scholar]
  129. Kim C.K. Lee Y.R. Ong L. Gold M. Kalali A. Sarkar J. Alzheimer’s disease: Key insights from two decades of clinical trial failures. J. Alzheimers Dis. 2022 87 1 83 100 10.3233/JAD‑215699 35342092
    [Google Scholar]
  130. Sun Y. Sun J. Feng Y. Zhang Y. Li J. Wang F. Significant downregulation of Alzheimer’s amyloid-β levels enabled by engineered DNA nanomaterials. Fundam. Res. 2024 5 2241 2247 10.1016/j.fmre.2024.03.017
    [Google Scholar]
  131. Vaz M. Silvestre S. Alzheimer’s disease: Recent treatment strategies. Eur. J. Pharmacol. 2020 887 173554 10.1016/j.ejphar.2020.173554 32941929
    [Google Scholar]
  132. Fang C. Hernandez P. Liow K. Damiano E. Zetterberg H. Blennow K. Feng D. Chen M. Maccecchini M. Buntanetap, a novel translational inhibitor of multiple neurotoxic proteins, proves to be safe and promising in both Alzheimer’s and Parkinson’s patients. J. Prev. Alzheimers Dis. 2023 10 1 25 33 10.14283/jpad.2022.84 36641607
    [Google Scholar]
  133. Koch G. Motta C. Bonnì S. Pellicciari M.C. Picazio S. Casula E.P. Maiella M. Di Lorenzo F. Ponzo V. Ferrari C. Scaricamazza E. Caltagirone C. Martorana A. Effect of rotigotine vs placebo on cognitive functions among patients with mild to moderate Alzheimer disease. JAMA Netw. Open 2020 3 7 2010372 10.1001/jamanetworkopen.2020.10372 32667654
    [Google Scholar]
  134. Cheng Y. Lin L. Huang P. Zhang J. Pan X. Efficacy, safety, and response predictors of Astragalus in patients with mild to moderate Alzheimer’s disease: A study protocol of an assessor-blind, statistician-blind open-label randomized controlled trial. Contemp. Clin. Trials Commun. 2024 41 101339 10.1016/j.conctc.2024.101339 39176240
    [Google Scholar]
  135. Sato K. Iwatsubo T. Anti-amyloid antibody drugs as disease-modifying therapies for Alzheimer’s disease. Brain Nerve 2024 76 9 991 995 10.11477/mf.1416202723 39251217
    [Google Scholar]
  136. Meglio M. Eli Lilly’s remternetug demonstrates significant amyloid plaque removal in early-stage trial. 2023 Available from: https://www.neurologylive.com/view/eli-lilly-remternetug-demonstrates-significant-amyloid-plaque-removal-early-stage-trial
    [Google Scholar]
  137. Honig L.S. Sabbagh M.N. van Dyck C.H. Sperling R.A. Hersch S. Matta A. Giorgi L. Gee M. Kanekiyo M. Li D. Purcell D. Dhadda S. Irizarry M. Kramer L. Updated safety results from phase 3 lecanemab study in early Alzheimer’s disease. Alzheimers Res. Ther. 2024 16 1 105 10.1186/s13195‑024‑01441‑8 38730496
    [Google Scholar]
  138. Zhang Y. Chen H. Li R. Sterling K. Song W. Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future. Signal Transduct. Target. Ther. 2023 8 1 248 10.1038/s41392‑023‑01484‑7 37386015
    [Google Scholar]
  139. Zhao K. Li Z. Liu Q. Cheng Y. Barreto G.E. Liu R. Novel therapeutic target and drug discovery for neurological diseases. Front. Pharmacol. 2022 13 1042266 10.3389/fphar.2022.1042266 36278216
    [Google Scholar]
  140. Dreves M.A.E. van Harten A.C. Visser L.N.C. Rhodius-Meester H. Köhler S. Kooistra M. Papma J.M. Honey M.I.J. Blom M.M. Smets E.M.A. de Vugt M.E. Teunissen C.E. van der Flier W.M. Rationale and design of the ABOARD project (a personalized medicine approach for Alzheimer’s disease). Alzheimers Dement. 2023 9 2 12401 10.1002/trc2.12401 37287472
    [Google Scholar]
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Role and Mechanisms Underlying NEU1 in Alzheimer's Disease: A 
Pathogenetic and Therapeutic Perspective
Bentham Science Publishers ; https://doi.org/10.2174/011570159X379241251023081519
/content/journals/cn/10.2174/011570159X379241251023081519
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  • Article Type:     Review Article
Keywords: cholinergic hypothesis ; amyloid-beta (Aβ) ; neuraminidase 1 ; neurodegenerative disorder ; dementia ; Alzheimer's disease

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