Identification of bioactive peptides from a Brazilian kefir sample, and their anti-Alzheimer potential in Drosophila melanogaster

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art_MALTA_Identification_of_bioactive_peptides_from_a_Brazilian_kefir_2022.PDF (4.52 MB)
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16
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article
Data de publicação
2022
DOI
Scopus
PubMed
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Editora
NATURE RESEARCH
Autores
MALTA, S. M.
BATISTA, L. L.
SILVA, H. C. G.
FRANCO, R. R.
SILVA, M. H.
RODRIGUES, T. S.
CORREIA, L. I. V.
MARTINS, M. M.
ESPINDOLA, F. S.
Citação
SCIENTIFIC REPORTS, v.12, n.1, article ID 11065, p, 2022
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
Alzheimer’s disease (AD) is the most common form of dementia in the elderly, affecting cognitive, intellectual, and motor functions. Different hypotheses explain AD’s mechanism, such as the amyloidogenic hypothesis. Moreover, this disease is multifactorial, and several studies have shown that gut dysbiosis and oxidative stress influence its pathogenesis. Knowing that kefir is a probiotic used in therapies to restore dysbiosis and that the bioactive peptides present in it have antioxidant properties, we explored its biotechnological potential as a source of molecules capable of modulating the amyloidogenic pathway and reducing oxidative stress, contributing to the treatment of AD. For that, we used Drosophila melanogaster model for AD (AD-like flies). Identification of bioactive peptides in the kefir sample was made by proteomic and peptidomic analyses, followed by in vitro evaluation of antioxidant and acetylcholinesterase inhibition potential. Flies were treated and their motor performance, brain morphology, and oxidative stress evaluated. Finally, we performed molecular docking between the peptides found and the main pathology-related proteins in the flies. The results showed that the fraction with the higher peptide concentration was positive for the parameters evaluated. In conclusion, these results revealed these kefir peptide-rich fractions have therapeutic potential for AD. © 2022, The Author(s).
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https://observatorio.fm.usp.br/handle/OPI/55914
Referências
  1. Talwar P., Et al., Dissecting complex and multifactorial nature of Alzheimer’s disease pathogenesis: A clinical, genomic, and systems biology perspective, Mol. Neurobiol., 53, pp. 4833-4864, (2016)
  2. Weller J., Budson A., Portelius E., Reddy H., Current understanding of Alzheimer’s disease diagnosis and treatment, F1000Research, 7, (2018)
  3. Nichols E., Et al., Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019, Lancet Public Health, 7, pp. e105-e125, (2022)
  4. Breijyeh Z., Karaman R., Comprehensive review on Alzheimer’s disease: Causes and treatment, Molecules (Basel), 25, (2020)
  5. Jellinger K.A., Neuropathological assessment of the Alzheimer spectrum, J. Neural Transm., 127, pp. 1229-1256, (2020)
  6. Lane C.A., Hardy J., Schott J.M., Alzheimer’s disease, Eur. J. Neurol., 25, pp. 59-70, (2018)
  7. Sharma V.K., Et al., Dysbiosis and Alzheimer’s disease: A role for chronic stress?, Biomolecules, 11, (2021)
  8. Kowalski K., Mulak A., Brain-gut-microbiota axis in Alzheimer’s disease, J. Neurogastroenterol. Motil., 25, pp. 48-60, (2019)
  9. Bonfili L., Et al., Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels, Sci. Rep., 7, (2017)
  10. Wong C.B., Kobayashi Y., Xiao J., Probiotics for preventing cognitive impairment in Alzheimer’s disease, Gut Microbiota Brain Axis., (2018)
  11. Nielsen B., Gurakan G.C., Unlu G., Kefir: A multifaceted fermented dairy product, Probiot. Antimicrob. Proteins, 6, pp. 123-135, (2014)
  12. Plessas S., Et al., Microbiological exploration of different types of kefir grains, Ferment, 3, (2016)
  13. Batista L.L., Et al., Kefir metabolites in a fly model for Alzheimer’s disease, Sci. Rep., 11, (2021)
  14. Tsuda L., Lim Y.-M., Alzheimer’s disease model system using drosophila, Adv. Exp. Med. Biol., 1076, pp. 25-40, (2018)
  15. Chakraborty R., Et al., Characterization of a drosophila Alzheimer’s disease model: Pharmacological rescue of cognitive defects, PLoS ONE, 6, (2011)
  16. Jeon Y., Lee J.H., Choi B., Won S.Y., Cho K.S., Genetic dissection of Alzheimer’s disease using Drosophila models, Int. J. Mol. Sci., 21, (2020)
  17. Jeibmann A., Paulus W., Drosophila melanogaster as a model organism of brain diseases, Int. J. Mol. Sci., 10, pp. 407-440, (2009)
  18. Prussing K., Voigt A., Schulz J.B., Drosophila melanogaster as a model organism for Alzheimer’s disease, Mol. Neurodegener., 8, (2013)
  19. Tue N.T., Dat T.Q., Ly L.L., Anh V.D., Yoshida H., Insights from Drosophila melanogaster model of Alzheimer’s disease, Front. Biosci. Landmark, 25, pp. 134-146, (2020)
  20. Benzie I.F.F., Strain J.J., The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay, Anal. Biochem., 239, pp. 70-76, (1996)
  21. Khurana R., Et al., Mechanism of thioflavin T binding to amyloid fibrils, J. Struct. Biol., 151, pp. 229-238, (2005)
  22. Cao Y., Chtarbanova S., Petersen A.J., Ganetzky B., Dnr1 mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain, Proc. Natl. Acad. Sci., 110, pp. E1752-E1760, (2013)
  23. Tung M.-C., Et al., Kefir peptides alleviate high-fat diet-induced atherosclerosis by attenuating macrophage accumulation and oxidative stress in ApoE knockout mice, Sci. Rep., 10, pp. 1-15, (2020)
  24. Pimenta F.S., Et al., Mechanisms of action of kefir in chronic cardiovascular and metabolic diseases, Cell. Physiol. Biochem., 48, pp. 1901-1914, (2018)
  25. Hamida R.S., Et al., Kefir: A protective dietary supplementation against viral infection, Biomed. Pharmacother., 133, (2021)
  26. Bourrie B.C.T., Richard C., Willing B.P., Kefir in the prevention and treatment of obesity and metabolic disorders, Curr. Nutr. Rep., 9, pp. 184-192, (2020)
  27. Azizi N.F., Et al., Kefir and its biological activities, Foods, 10, (2021)
  28. Barao C.E., Et al., Growth kinetics of kefir biomass: Influence of the incubation temperature in milk, Chem. Eng. Trans., 75, pp. 499-504, (2019)
  29. Londero A., Hamet M.F., De Antoni G.L., Garrote G.L., Abraham A.G., Kefir grains as a starter for whey fermentation at different temperatures: Chemical and microbiological characterisation, J. Dairy Res., 79, pp. 262-271, (2012)
  30. Dallas D.C., Et al., Peptidomic analysis reveals proteolytic activity of kefir microorganisms on bovine milk proteins, Food Chem., 197, pp. 273-284, (2016)
  31. Amorim F.G., Et al., Identification of new bioactive peptides from Kefir milk through proteopeptidomics: Bioprospection of antihypertensive molecules, Food Chem., 282, pp. 109-119, (2019)
  32. Fan M., Et al., Isolation and identification of novel casein-derived bioactive peptides and potential functions in fermented casein with Lactobacillus helveticus, Food Sci. Hum. Wellness, 8, pp. 156-176, (2019)
  33. Marcone S., Belton O., Fitzgerald D.J., Milk-derived bioactive peptides and their health promoting effects: A potential role in atherosclerosis, Br. J. Clin. Pharmacol., 83, pp. 152-162, (2017)
  34. Nagpal R., Et al., Bioactive peptides derived from milk proteins and their health beneficial potentials: An update, Food Funct., 2, pp. 18-27, (2011)
  35. Kaur D., Et al., Multifaceted Alzheimer’s disease: Building a roadmap for advancement of novel therapies, Neurochem. Res., (2021)
  36. Zhao Y., Zhao B., Oxidative stress and the pathogenesis of Alzheimer’s disease, Oxid. Med. Cell. Longev., (2013)
  37. Nalivaeva N., Turner A., AChE and the amyloid precursor protein (APP)—Cross-talk in Alzheimer’s disease, Chem. Biol. Interact., 259, pp. 301-306, (2016)
  38. Tonnies E., Trushina E., Oxidative stress, synaptic dysfunction, and Alzheimer’s disease, J. Alzheimers Dis., 57, pp. 1105-1121, (2017)
  39. Huang W., Zhang X., Chen W., Role of oxidative stress in Alzheimer’s disease, Biomed. Reports, 4, pp. 519-522, (2016)
  40. Birla H., Minocha T., Kumar G., Misra A., Singh S.K., Role of oxidative stress and metal toxicity in the progression of Alzheimer’s disease, Curr. Neuropharmacol., 18, pp. 552-562, (2020)
  41. Ferreira-Vieira T.H., Guimaraes I.M., Silva F.R., Ribeiro F.M., Alzheimer’s disease: Targeting the cholinergic system, Curr. Neuropharmacol., 14, (2016)
  42. Grodzicki W., Dziendzikowska K., The role of selected bioactive compounds in the prevention of Alzheimer’s disease, Antioxidants, 9, (2020)
  43. Sousa J.C.E., Santana A.C.F., Magalhaes G.J.P., Resveratrol in Alzheimer’s disease: A review of pathophysiology and therapeutic potential, Arq. Neuropsiquiatr., 78, pp. 501-511, (2020)
  44. Forlenza O.V., Tratamento farmacológico da doença de Alzheimer, Arch. Clin. Psychiatry (São Paulo), 32, pp. 137-148, (2005)
  45. Yiannopoulou K.G., Papageorgiou S.G., Current and future treatments for Alzheimer’s disease, Ther. Adv. Neurol. Disord., 6, (2013)
  46. Wang X., Et al., Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models, BMC Complement. Altern. Med., 14, (2014)
  47. Chiu W.Y.V., Et al., GULP1/CED-6 ameliorates amyloid-β toxicity in a Drosophila model of Alzheimer’s disease, Oncotarget, 8, pp. 99274-99283, (2017)
  48. da Costa Silva J.R., Et al., Differential gene expression by RNA-seq during Alzheimer’s disease-like progression in the Drosophila melanogaster model, Neurosci. Res., (2022)
  49. Yu Z., Et al., Identification and molecular docking study of fish roe-derived peptides as potent BACE 1, AChE, and BChE inhibitors, Food Funct., 11, pp. 6643-6651, (2020)
  50. Dvir H., Silman I., Harel M., Rosenberry T.L., Sussman J.L., Acetylcholinesterase: From 3D structure to function, Chem. Biol. Interact., 187, pp. 10-22, (2010)
  51. Hong L., Et al., Structure of the protease domain of memapsin 2 (β-secretase) complexed with inhibitor, Science, 290, pp. 150-153, (2000)
  52. Hong L., Tang J., Flap position of free memapsin 2 (β-secretase), a model for flap opening in aspartic protease catalysis†,‡, Biochemistry, 43, pp. 4689-4695, (2004)
  53. James M.N., Sielecki A., Salituro F., Rich D.H., Hofmann T., Conformational flexibility in the active sites of aspartyl proteinases revealed by a pepstatin fragment binding to penicillopepsin, Proc. Natl. Acad. Sci., 79, pp. 6137-6141, (1982)
  54. Shimizu H., Et al., Crystal structure of an active form of BACE1, an enzyme responsible for amyloid β protein production, Mol. Cell. Biol., 28, pp. 3663-3671, (2008)
  55. Ray B., Et al., Rivastigmine modifies the α-secretase pathway and potentially early Alzheimer’s disease, Transl. Psychiatry, 10, pp. 1-17, (2020)
  56. Luheshi L.M., Et al., Systematic in vivo analysis of the intrinsic determinants of amyloid β pathogenicity, PLoS Biol., 5, (2007)
  57. Xiao Y., Et al., Aβ(1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer’s disease, Nat. Struct. Mol. Biol., 22, pp. 499-505, (2015)
  58. Rhee I.K., Van De Meent M., Ingkaninan K., Verpoorte R., Screening for acetylcholinesterase inhibitors from Amaryllidaceae using silica gel thin-layer chromatography in combination with bioactivity staining, J. Chromatogr. A, 915, pp. 217-223, (2001)
  59. Gargano J.W., Martin I., Bhandari P., Grotewiel M.S., Rapid iterative negative geotaxis (RING): A new method for assessing age-related locomotor decline in Drosophila, Exp. Gerontol., 40, pp. 386-395, (2005)
  60. Ellman G.L., Courtney K.D., Andres V., Featherstone R.M., A new and rapid colorimetric determination of acetylcholinesterase activity, Biochem. Pharmacol., 7, pp. 88-95, (1961)
  61. Westfall S., Lomis N., Prakash S., A novel synbiotic delays Alzheimer’s disease onset via combinatorial gut-brain-axis signaling in Drosophila melanogaster, PLoS ONE, 14, (2019)

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Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - LIM/13