Acta Scientific Microbiology (ISSN: 2581-3226)

Research Article Volume 5 Issue 8

Nuclear Amyloid Fibrils Detected in Human SH-SY5Y Cells in Presence of Aβ1-42 and LPS

Anna Lia Asti1*, Nicoletta Marchesi2, Teresa Rampino1, Marilena Gregorini1, Marcella Reguzzoni3, Lorena Vailati4, Alessia Pascale2

1Unit of Nephrology, Dialysis and Transplantation, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy

2Department of Drug Sciences, Pharmacology Section, University of Pavia, Pavia, Italy

3Department of Medicine and Surgery, University of Insubria, Varese, Italy

4Department of Molecular Medicine, Fondazione IRCCS, Policlinico San Matteo, Pavia, Italy

*Corresponding Author: Anna Lia Asti, Unit of Nephrology, Dialysis and Transplantation, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy.

Received: July 13, 2022; Published: July 21, 2022


Amyloid-β peptide (Aβ) represents the main component of amyloid plaques in Alzheimer’s disease (AD); Aβ belongs to the group of antimicrobial peptides (AMPs) small peptides that kill pathogens through their antimicrobial activity and also have affinity for bacterial lipopolysaccharide (LPS). If amyloid is part of the antimicrobial mechanism of Aβ, fibrillar material would also be expected to accumulate as long as the innate immune system, correctly or incorrectly perceives an infection. Repeated reactivations of the chronic latent infection are constantly producing new Aß peptide, this situation lasts for a long time in the decades preceding the manifestation of AD, progressively leading to neurodegeneration and neuroinflammation. Aim of this work was to evaluate the concomitant synergizing action of Aβ1-42 and LPS in human SH-SY5Y cells; AMPs and LPS have an amphipatic structure that is able to form heterogeneous micelles, in this way LPS acts as a fibrillogenesis promoter, Furthermore, depending on peptide concentration, the action of Aβ as AMP can be bacteriostatic or bactericidal.

Keywords: Amyloid-beta (Aβ); Bacterial Lipopolysaccharide (LPS); Antimicrobial Peptide (AMP); Blood Brain Barrier (BBB); Alzheimer’s Disease (AD)


  1. Soscia SJ., et al. “The Alzheimer’s disease associated amyloid beta-protein is an antimicrobial peptide”. PLoS One 5 (2010): 1-10.
  2. Lee EY., et al. “Functional Reciprocity of Amyloids and Antimicrobial Peptides: Rethinking the Role of Supramolecular Assembly in Host Defense, Immune Activation, and Inflammation”. Frontiers in Immunology 11 (2020): 1629.
  3. Gosztyla ML., et al. “Alzheimer's Amyloid-β is an Antimicrobial Peptide: A Review of the Evidence”. Journal of Alzheimer's Disease4 (2018): 1495-1506.
  4. Dorin JR and Davidson DJ. “Mammalian antimicrobial peptides: defensins and cathelicidins”. Molecular Medical Microbiology 1 (2014): 539-565.
  5. Kościuczuk EM., et al. “Cathelicidins: family of antimicrobial peptides. A review”. Molecular Biology Reports 12 (2012): 10957-10970.
  6. Serpell LC., et al. “The protofilament substructure of amyloid fibrils”. Journal of Molecular Biology 300 (2000): 1033-1039.
  7. De Chiara G., et al. “Infectious agents and neurodegeneration”. Molecular Neurobiology 46 (2012): 614-638.
  8. Fulop T., et al. “Can an Infection Hypothesis Explain the Beta Amyloid Hypothesis of Alzheimer’s Disease?” Frontiers in Aging Neuroscience 24 (2018): 72.
  9. Heneka MT., et al. “Innate immunity in Alzheimer's disease”. Nature Immunology3 (2015): 229-236.
  10. Crack PJ and Bray PJ. “Toll-like receptors in the brain and their potential roles in neuropathology”. Immunology and Cell Biology 85 (2007): 476-480.
  11. Mariathasan S., et al. “Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf”. Nature 6996 (2004): 213-218.
  12. Kaushal V., et al. “Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation”. Cell Death Difference10 (2015): 1676-1686.
  13. Gibson FC III., et al. “Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice”. Circulation 109 (2004): 2801-2806.
  14. Zaiou M. “Multifunctional antimicrobial peptides: therapeutic targets in several human diseases”. Journal of Molecular Medicine 85 (2007): 317-329.
  15. Kumar DK., et al. “Alzheimer's disease: the potential therapeutic role of the natural antibiotic amyloid-β peptide”. Neurodegenerative Disease Management 5 (2016): 345-348.
  16. Miklossy J and Martins RN. “Chronic inflammation and amyloidogenesis in Alzheimer’s disease: the emerging role of infection”. Journal of Alzheimer's Disease (2008): 13-357.
  17. Miklossy J. “Emerging role of pathogens in Alzheimer’s disease”. Expert Reviews in Molecular Medicine 13 (2011).
  18. Brown GC. “The endotoxin hypothesis of neurodegeneration”. Journal of Neuroinflammation 16 (2019): 180.
  19. Seong-Cheol Park., et al. “Functional characterization of alpha-synuclein protein with antimicrobial activity”. Biochemical and Biophysical Research Communications 478 (2016): 924e928.
  20. Balin BJ., et al. “Identification and localization of Chlamydia pneumoniae in the Alzheimer’s brain”. Medical Microbiology and Immunology 187 (1998): 23-42.
  21. Asti A and Gioglio L. “Can a bacterial endotoxin be a key factor in the kinetics of amyloid fibril formation?” Journal of Alzheimer's Disease1 (2014): 169-179.
  22. Langford D and Masliah E. “The emerging role of infectious pathogens in neurodegenerative diseases”. Experimental Neurology 184 (2003): 553-555.
  23. Zhan X., et al. “Lipopolysaccharide Associates with Amyloid Plaques, Neurons and Oligodendrocytes in Alzheimer’s Disease Brain: A Review”. Frontiers in Aging Neuroscience 10 (2018): 42.
  24. Roberts JA., et al. “A brain proteomic signature of incipient Alzheimer's disease in young APOE ε4 carriers identifies novel drug targets”. Science Advances 46 (2021): eabi8178.
  25. Pang CP and Baum L. “Lipoproteins and Related Molecules in Alzheimer’s Disease”. Microscopy Research and Technique 50 (2000): 259-260.
  26. Paik S., et al. “Somatostatin Ameliorates β-Amyloid-Induced Cytotoxicity via the Regulation of CRMP2 Phosphorylation and Calcium Homeostasis in SH-SY5Y Cells”. Biomedicines1 (2021): 27.
  27. Soreghan B., et al. “Surfactant properties of Alzheimer’s A beta peptides and the mechanism of amyloid aggregation”. Journal of Biological Chemistry 269 (1994): 28551-28554.
  28. Harris JR. “In vitro fibrillogenesis of the amyloid B1−42 peptide: Cholesterol potentiation and aspirin inhibition”. Micron 33 (2002): 609-626.
  29. Pirc K and Ulrih NP. “A-Synuclein interactions with phospholipid model membranes: key roles for electrostatic interactions and lipid-bilayer structure”. Biochimica et Biophysica Acta 1848 (2015): 2002e2012.
  30. Aisenbrey C., et al. “How is protein aggregation in amyloidogenic diseases modulated by biological membranes”. European Biophysics Journal 37 (2008): 247-255.
  31. Dikiy I and Eliezer D. “Folding and misfolding of alpha-synuclein on membranes”. Biochimica et Biophysica Acta 1818 (2012): 1013-1018.
  32. Lomakin A., et al. “On the nucleation and growth of amyloid ,8-protein fibrils: Detection of nuclei and quantitation of rate constants”. Proceedings of the National Academy of Sciences 93 (1996): 1125-1129.
  33. Sun Y Shan. “Inhibitory effects of antimicrobial peptides on lipopolysaccharide-induced inflammation”. Mediators Inflammation (2015): 167572.
  34. Caillon L., et al. “Biophysical investigation of the membrane-disrupting mechanism of the antimicrobial and amyloid-like peptide dermaseptin S9”. PLoS One10 (2013): e75528.
  35. Mawanda F and Wallace R. “Can Infections Cause Alzheimer’s Disease?” Epidemiology Review 35 (2013): 161-180.
  36. Asti A., et al. “The synergic action of amyloid-β peptide and LPS in amyloid plaque formation”. Archives of Medical Science - Aging 2 (2019): e10-e19.
  37. Lee M., et al. “Human antimicrobial peptide LL-37 induces glial-mediated neuroinflammation”. Biochemical Pharmacology 94 (2015): 130-141.
  38. Suzuki K., et al. “Bacterial lipopolysaccharide and antimicrobial LL-37 enhance ICAM-1 expression and NF-κB p65 phosphorylation in senescent endothelial cells”. International Journal of Molecular Medicine 44 (2019): 1187-1196.
  39. Engelberg Y and Landau M. “The Human LL-37 (17-29) antimicrobial peptide reveals a functional supramolecular structure”. Nature Communication1 (2020): 3894.
  40. De Lorenzi E., et al. “Evidence that the Human Innate Immune Peptide LL-37 may be a Binding Partner of Amyloid-β and Inhibitor of Fibril Assembly”. Journal of Alzheimer's Disease4 (2017): 1213-1226.
  41. Ciornei CD., et al. “Human antimicrobial peptide LL-37 is present in atherosclerotic plaques and induces death of vascular smooth muscle cells: a laboratory study”. BMC Cardiovascular Disorder 6 (2006): 49.
  42. Yang B., et al. “Significance of LL-37 on Immunomodulation and Disease Outcome”. BioMed Research International (2020): 8349712.
  43. Grewal SL and Moazed D. “Heterochromatin and epigenetic control of gene expression”. Science 301 (2003): 798-802.
  44. Duggan NM and Tang ZI. “The Formation of Heterochromatin”. Nature Education 9 (2010): 5.
  45. Lippman Z and Martienssen R. “The role of RNA interference in heterochromatic silencing”. Nature 431 (2004): 364-370.
  46. Roy S and Banerjee SS. “Gut microbiota in neurodegenerative disorders”. Journal of Neuroimmunology 328 (2019): 98-104100.
  47. Bourgade K., et al. “Anti-Viral Properties of Amyloid-β Peptides”. Journal of Alzheimer's Disease 3 (2016): 859-878.
  48. Spitzer P., et al. “Amyloidogenic amyloid-β-peptide variants induce microbial agglutination and exert antimicrobial activity”. Scientific Report 6 (2016): 32228.


Citation: Anna Lia Asti., et al. “Nuclear Amyloid Fibrils Detected in Human SH-SY5Y Cells in Presence of Aβ1-42 and LPS". Acta Scientific Microbiology 5.8 (2022): 90-96.


Copyright: © 2022 Anna Lia Asti., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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