1. На главную
  2. Электронные версии
  3. Цитология
  4. T. 65, № 4, 2023

Цитология, 2023, T. 65, № 4, стр. 323-338

Молекулярные механизмы, лежащие в основе болезней Альцгеймера и Паркинсона, и потенциальная возможность их нейтрализации

О. В. Невзглядова 1, *, Е. В. Михайлова 1, Т. Р. Сойдла 1

1 Институт цитологии РАН
194064 Санкт-Петербург, Россия

* E-mail: oneva43@yahoo.com

Поступила в редакцию 12.12.2022
После доработки 25.01.2023
Принята к публикации 08.02.2023

Аннотация

Под действием внешних и внутренних факторов в клетках неизбежно возникают разные измененные белковые формы. С возрастом активность шаперонов и других компонентов клеточного контроля за качеством белка снижается. Это сопровождается накоплением неправильно уложенных белков с измененной конформацией. Наиболее драматично для клетки превращение активного растворимого белка в амилоидное нерастворимое и неактивное состояние. Считается, что такое изменение конформации белка лежит в основе процесса нейродегенерации. Хотя этот процесс интенсивно изучается, многие детали нейродегенерации остаются непроясненными. В настоящем обзоре мы приводим наиболее принятые в настоящее время молекулярные механизмы патогенеза самых распространенных нейродегенеративных заболеваний – Альцгеймера и Паркинсона. Они включают в себя последовательные реакции бета-амило́ида и альфа-синуклеина с мембранными рецепторами и модулируются фазовым разделением и кросс-сидингом с другими клеточными прионами. Особое внимание уделяется натуральным полифункциональным соединениям, как наиболее терапевтически перспективным.

Ключевые слова: амилоид, антиамилоидные соединения, немембранные органеллы, кросс-сидинг

Список литературы

  1. Зубова С.Г. 2019. Многоликость аутофагии и ее неоднозначная роль в биологических процессах. Цитология. Т. 61. № 12. С. 941. (Zubova S.G. 2019. The diversity of autophagy and its controversial role in biological processes. Tsitologiya. V. 61. № 12. P. 941). https://doi.org/10.1134/S0041377119120095

  2. Agarwal A., Arora L., Rai S.K., Avni A., Mukhopadhyay S. 2022. Spatiotemporal modulations in heterotypic condensates of prion and α-synuclein control phase transitions and amyloid conversion. Nature Commun. V. 13. P. 1. https://doi.org/10.1038/s41467-022-28797-5

  3. Adem K., Shanti A., Srivastava A., Homouz D., Thomas S.A., Khair M., Stefanini C., Chan V., Kim T.Y., Lee S. 2022. Linking Alzheimer’s disease and type 2 diabetes: characterization and inhibition of cytotoxic Aβ and IAPP hetero-aggregates. Front. Mol. Biosci. V. 9. P. 842582. https://doi.org/10.3389/fmolb.2022.842582

  4. Alam P., Bousset L., Melki R., Otzen D.E. 2019. α-Synuclein oligomers and fibrils: a spectrum of species, a spectrum of toxicities. J. Neurochem. V. 150. P. 522. https://doi.org/10.1111/jnc.14808

  5. Ashrafian H., Zadeh E.H., Khan R.H. 2021. Review on Alzheimer’s disease: inhibition of amyloid beta and tau tangle formation. Int. J. Biol. Macromol. V. 167. P. 382. https://doi.org/10.1016/j.ijbiomac.2020.11.192

  6. Baba M., Nakajo S., Tu P.H., Tomita T., Nakaya K., Lee V.M., Trojanowski J.Q., Iwatsubo T. 1998. Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies. Am. J. Pathol. V. 152. P. 879.

  7. Badiola N., de Oliveira R.M., Herrera F., Guardia-Laguarta C., Gonçalves S.A., Pera M., Suárez-Calvet M., Clarimon J., Outeiro T.F., Lleó A. 2011. Tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy. PLoS One. V. 6. P. e26609. https://doi.org/10.1371/journal.pone.0026609

  8. Banerjee D., Sanyal S. 2014. Protein folding activity of the ribosome (PFAR) — a target for antiprion compounds. Viru-ses. V. 6. P. 3907. https://doi.org/10.3390/v6103907

  9. Barbier P., Zejneli O., Martinho M., Lasorsa A., Belle V., Smet-Nocca C., Tsvetkov P.O., Devred F., Landrieu I. 2019. Role of Tau as a microtubule-associated protein: structural and functional aspects. Front. Aging Neurosci. V. 11. P. 204. https://doi.org/10.3389/fnagi.2019.00204

  10. Barbitoff Y.A., Matveenko A.G., Moskalenko S.E., Zemlyanko O.M., Newnam G.P., Patel A., Chernova T.A., Chernoff Y.O., Zhouravleva G.A. 2017. To CURe or not to CURe? Differential effects of the chaperone sorting factor Cur1 on yeast prions are mediated by the chaperone Sis1. Mol. Microbiol. V. 105. P. 242. https://doi.org/10.1111/mmi.13697

  11. Beeg M., Stravalaci M., Romeo M., Carrá A.D., Cagnotto A., Rossi A., Diomede L., Salmona M., Gobbi M. 2016. Clusterin binds to Aβ1-42 oligomers with high affinity and interferes with peptide aggregation by inhibiting primary and secondary nucleation. J. Biol. Chem. V. 291. P. 6958. https://doi.org/10.1074/jbc.M115.689539

  12. Beldona V., Patel A., Patel K., Abraham N., Halvorsen A., Liu A., Mannem N., Renganathan G. 2022. Natural product polyphenol inhibition of amyloid-β aggregation. J. High School Sci. V. 32281. http://jhss.scholasticahq.com

  13. Bennett R.E., DeVos S.L., Dujardin S., Corjuc B., Gor R., Gonzalez J., Roe A.D., Frosch M.P., Pitstick R., Carlson G.A., Hyman B.T. 2017. Enhanced tau aggregation in the presence of amyloid β. Am. J. Pathol. V. 187. P. 1601. https://doi.org/10.1016/j.ajpath.2017.03.011

  14. Bharadwaj P., Solomon T., Sahoo B.R., Ignasiak K., Gaskin S., Rowles J., Verdile G., Howard M.J., Bond C.S., Ramamoorthy A., Martins R.N., Newsholme P. 2020. Amylin and beta amyloid proteins interact to form amorphous heterocomplexes with enhanced toxicity in neuronal cells. Sci. Rep. V. 10. P. 10356. https://doi.org/10.1038/s41598-020-66602-9

  15. Blondel M., Soubigou F., Evrard J., Nguyen P.H., Hasin N., Chédin S., Gillet R., Contesse M.A., Friocourt G., Stahl G., Jones G.W., Voisset C. 2016. Protein folding activity of the ribosome is involved in yeast prion propagation. Sci. Rep. V. 6. P. 32117. https://doi.org/10.1038/srep32117

  16. Botstein D., Fink G.R. 2011. Yeast: an experimental organism for 21st century biology. Genetics. V. 189. P. 695. https://doi.org/10.1534/genetics.111.130765

  17. Braak H., Alafuzoff I., Arzberger T., Kretzschmar H., Del Tredici K. 2006. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. V. 112. P. 389. https://doi.org/10.1007/s00401-006-0127-z

  18. Bush A.I. 2003. The metallobiology of Alzheimer’s disease. Trends Neurosci. V. 26. P. 207. https://doi.org/10.1016/S0166-2236(03)00067-5

  19. Candreva J., Chau E., Rice M.E., Kim J.R. 2020. Interactions between soluble species of β-Amyloid and α-Synuclein promote oligomerization while inhibiting fibrillization. Biochemistry. V. 59. P. 425. https://doi.org/10.1021/acs.biochem.9b00655

  20. Cascella R., Bigi A., Cremades N., Cecchi C. 2022. Effects of oligomer toxicity, fibril toxicity and fibril spreading in synucleinopathies. Cell Mol. Life Sci. V. 79. P. 174. https://doi.org/10.1007/s00018-022-04166-9

  21. Cascella R., Chen S.W., Bigi A., Camino J.D., Xu C.K., Dobson C.M., Chiti F., Cremades N., Cecchi C. 2021. The release of toxic oligomers from α-synuclein fibrils induces dysfunction in neuronal cells. Nat. Commun. V. 12. P. 1814. https://doi.org/10.1038/s41467-021-21937-3

  22. Cheng A., Wang Y.F., Shinoda Y., Kawahata I., Yamamoto T., Jia W.B., Yamamoto H., Mizobata T., Kawata Y., Fukunaga K. 2022. Fatty acid-binding protein 7 triggers α-synuclein oligomerization in glial cells and oligodendrocytes associated with oxidative stress. Acta Pharmacol. Sin. V. 43. P. 552. https://doi.org/10.1038/s41401-021-00675-8

  23. Chernoff Y.O., Grizel A.V., Rubel A.A., Zelinsky A.A., Chandramowlishwaran P., Chernova T.A. 2020. Application of yeast to studying amyloid and prion diseases. Adv. Genet. V. 105. P. 293. https://doi.org/10.1016/bs.adgen.2020.01.002

  24. Chernova T.A., Chernoff Y.O., Wilkinson K.D. 2019. Yeast models for amyloids and prions: environmental modulation and drug discovery. Molecules. V. 24. P. 3388. https://doi.org/10.3390/molecules24183388

  25. Choudhary V., Ojha N., Golden A., Prinz W.A. 2015. A conserved family of proteins facilitates nascent lipid droplet budding from the ER. J. Cell Biol. V. 211. P. 261. https://doi.org/10.1083/jcb.201505067

  26. Cohen S.I.A., Arosio P., Presto J., Kurudenkandy F.R., Biverstal H., Dolfe L., Dunning C., Yang X., Frohm B., Vendruscolo M., Johansson J., Dobson C.M., Fisahn A., Knowles T.P.J., Linse S. 2015. A molecular chaperone breaks the catalytic cycle that generates toxic Aβ-oligomers. Nat. Struct. Mol. Biol. V. 22. P. 207. https://doi.org/10.1038/nsmb.2971

  27. Colla E., Coune P., Liu Y., Pletnikova O., Troncoso J.C., Iwatsubo T., Schneider B.L., Lee M.K. 2012. Endoplasmic reticulum stress is important for the manifestations of α-synucleinopathy in vivo. J. Neurosci. V. 32. P. 3306. https://doi.org/10.1523/JNEUROSCI.2617-07.2007

  28. Desplats P., Lee H.J., Bae E.J., Patrick C., Rockenstein E., Crews L., Spencer B., Masliah E., Lee S.J. 2009. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc. Natl. Acad. Sci. USA. V. 106. P. 13010. https://doi.org/10.1073/pnas.0903691106

  29. Doody R.S., Gavrilova S.I., Sano M., Thomas R.G., Aisen P.S., Bachurin S.O., Seely L., Hung D., Dimebon I. 2008. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer’s disease: a randomised, double-blind, placebo-controlled study. Lancet. V. 372. P. 207. https://doi.org/10.1016/S0140-6736(08)61074-0

  30. Dujardin S., Bégard S., Caillierez R., Lachaud C., Delattre L., Carrier S., Loyens A., Galas M.-C., Bousset L., Melki R., Auregan G., Hantraye P., Brouillet E., Buee L., Colin M. 2014. Ectosomes: a new mechanism for non-exosomal secretion of Tau protein. PLoS One. V. 9. P. e100760. https://doi.org/10.1371/journal.pone.0100760

  31. Ehrnhoefer D.E., Bieschke J., Boeddrich A., Herbst M., Masino L., Lurz R., Engemann S., Pastore A., Wanker E.E. 2008. EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat. Struct. Mol. Biol. V. 15. P. 558. https://doi.org/10.1038/nsmb.1437

  32. Emmanouilidou E., Melachroinou K., Roumeliotis T., Garbis S.D., Ntzouni M., Margaritis L.H., Stefanis L., Vekrellis K. 2010. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J. Neurosci. V. 30. P. 6838. https://doi.org/10.1523/JNEUROSCI.5699-09.2010

  33. Faria C., Jorge C.D., Borges N., Tenreiro S., Outeiro T.F., Santos H. 2013. Inhibition of formation of α-synuclein inclusions by mannosyl glycerate in a yeast model of Parkinson’s disease. Biochim. Biophys. Acta. V. 1830. P. 4065. https://doi.org/10.1016/j.bbagen.2013.04.015

  34. Fernandes J.T., Tenreiro S., Gameiro A., Chu V., Outeiro T.F., Conde J.P. 2014. Modulation of α-synuclein toxicity in yeast using a novel microfluidic-based gradient generator. Lab. Chip. V. 14. P. 3949. https://doi.org/10.1039/C4LC00756E

  35. Fernandez-Funez P., Sanchez-Garcia J., de Mena L., Zhang Y., Levites Y., Khare S., Golde T.E., Rincon-Limas D.E. 2016. Holdase activity of secreted Hsp70 masks amyloid-β42 neurotoxicity in Drosophila. Proc. Natl. Acad. Sci. USA. V. 113. P. E5212. https://doi.org/10.1073/pnas.1608045113

  36. Franić D., Zubčić K., Boban M. 2021. Nuclear ubiquitin-proteasome pathways in proteostasis maintenance. Biomolecules. V. 4. P. 54. https://doi.org/10.3390/biom11010054

  37. Fusco G., Chen S.W., Williamson P.T.F., Cascella R., Perni M., Jarvis J.A., Cecchi C., Vendruscolo M., Chiti F., Cremades N., Ying L., Dobson C.M., De Simone A. 2017. Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers. Science. V. 358. P. 1440. https://doi.org/10.1126/science.aan6160

  38. Gauci A.J., Caruana M., Giese A., Scerri C., Vassallo N. 2011. Identification of polyphenolic compounds and black tea extract as potent inhibitors of lipid membrane destabilization by Aβ42 aggregates. J. Alzheimers Dis. V. 27. P. 767. https://doi.org/10.3233/JAD-2011-111061

  39. Gomes L.M.F., Bataglioli J.C., Storr T. 2020. Metal complexes that bind to the amyloid-β peptide of relevance to Alzheimer’s disease. Coordinat. Chem. Rev. V. 412. P. 213 255. https://doi.org/10.1016/j.ccr.2020.213255

  40. Grelle G., Otto A., Lorenz M., Frank R.F., Wanker E.E., Bieschke J. 2011. Black tea theaflavins inhibit formation of toxic amyloid-beta and alpha-synuclein fibrils. Biochemistry. V. 50. P. 10624. https://doi.org/10.1021/bi2012383

  41. Habchi J., Chia S., Galvagnion C., Michaels T.C.T., Bellaiche M.M.J., Ruggeri F.S., Sanguanini M., Idini I., Kumita J.R., Sparr E., Linse S., Dobson C.M., Knowles T.P.J., Vendruscolo M. 2018. Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes. Nat. Chem. V. 10. P. 673. https://doi.org/10.1038/s41557-018-0031-x

  42. Hachiya N., Fulek M., Zajączkowska K., Kurpas D., Trypka E., Leszek J. 2021. Cellular prion protein and amyloid-β oligomers in Alzheimer’s disease – there are connections? Preprints. 2021050032. https://doi.org/10.20944/preprints202105.0032.v1

  43. Hamano T., Hayashi K., Shirafuji N., Nakamoto Y. 2018. The implications of autophagy in Alzheimer’s disease. Curr. Alzheimer Res. V. 15. P. 1283. https://doi.org/10.2174/1567205015666181004143432

  44. Hardenberg M., Horvath A., Ambrus V., Fuxreiter M., Vendruscolo M. 2020. Widespread occurrence of the droplet state of proteins in the human proteome. Proc. Natl. Acad. Sci. USA. V. 117. P. 33254. https://doi.org/10.1073/pnas.2007670117

  45. Hardenberg M.C., Sinnige T., Casford S., Dada S.T., Poudel C., Robinson E.A., Fuxreiter M., Kaminksi C.F., Kaminski Schierle G.S., Nollen E.A.A., Dobson C.M., Vendruscolo M. 2021. Observation of an α-synuclein liquid droplet state and its maturation into Lewy body-like assemblies. J. Mol. Cell Biol. V. 13. P. 282. https://doi.org/10.1093/jmcb/mjaa075

  46. Hashimoto M., Masliah E. 1999. Alpha-synuclein in Lewy Body Disease and Alzheimer’s Disease. Brain Pathology. V. 9. P. 707. https://doi.org/10.1111/j.1750-3639.1999.tb00552.x

  47. Hevroni B.L., Major D.T., Dixit M., Mhashal A.R., Das S., Fischer B. 2016. Nucleoside-2′, 3′/3′, 5′-bis (thio) phosphate antioxidants are also capable of disassembly of amyloid beta 42-Zn (ii)/Cu (ii) aggregates via Zn (ii)/Cu (ii)-chelation. Organic Biomol. Chem. V. 14. P. 4640. https://goi.org/10/1039/C6OB00613B

  48. Hideshima M., Kimura Y., Aguirre C., Kakuda K., Takeuchi T., Choong C.J., Doi J., Nabekura K., Yamaguchi K., Nakajima K., Baba K., Nagano S., Goto Y., Nagai Y., Mochizuki H., Ikenaka K. 2022. Two-step screening method to identify α-synuclein aggregation inhibitors for Parkinson’s disease. Sci. Rep. V. 12. P. 351. https://doi.org/10.1038/s41598-021-04131-9

  49. Hijaz B.A., Volpicelli-Daley L.A. 2020. Initiation and propagation of α-synuclein aggregation in the nervous system. Mol. Neurodegener. V. 15. P. 19. https://doi.org/10.1186/s13024-020-00368-6

  50. Hillen H. 2019. The beta amyloid dysfunction (BAD) hypothesis for Alzheimer’s disease. Front. Neurosci. V. 13. P. 1154. https://doi.org/10.3389/fnins.2019.01154

  51. Hurst L.R., Fratti R.A. 2020. Lipid rafts, sphingolipids, and ergosterol in yeast vacuole fusion and maturation. Front. Cell Dev. Biol. V. 8. P. 539. https://doi.org/10.3389/fcell.2020.00539

  52. Jackson K., Barisone G.A., Diaz E., Jin L.W., DeCarli C., Despa F. 2013. Amylin deposition in the brain: a second amyloid in Alzheimer disease? Ann. Neurol. V. 74. P. 517. https://doi.org/10.1002/ana.23956

  53. Jacobs H.I.L., Hedden T., Schultz A.P., Sepulcre J., Perea R.D., Amariglio R.E., Papp K.V., Rentz D.M., Sperling R.A., Johnson K.A. 2018. Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals. Nat. Neurosci. V. 21. P. 424. https://doi.org/10.1038/s41593-018-0070-z

  54. Jacquier N., Choudhary V., Mari M., Toulmay A., Reggiori F., Schneiter R. 2011. Lipid droplets are functionally connected to the endoplasmic reticulum in Saccharomyces cerevisiae. J. Cell Sci. V. 124. P. 2424. https://doi.org/10.1242/jcs.076836

  55. Jomova K., Vondrakova D., Lawson M., Valko M. 2010. Metals, oxidative stress and neurodegenerative disorders. Mol. Cell Biochem. V. 345. P. 91. https://doi.org/10.1007/s11010-010-0563-x

  56. Kalaitzakis M.E., Graeber M.B., Gentleman S.M., Pearce R.K. 2008. Striatal beta-amyloid deposition in Parkinson disease with dementia. J. Neuropathol. Exp. Neurol. V. 67. P. 155. https://doi.org/10.1097/NEN.0b013e31816362aa

  57. Kieran D., Hafezparast M., Bohnert S., Dick J.R., Martin J., Schiavo G., Fisher E.M., Greensmith L. 2005. A mutation in dynein rescues axonal transport defects and extends the life span of ALS mice. J. Cell Biol. V. 169. P. 561. https://doi.org/10.1083/jcb.200501085

  58. König A.S., Rösener N.S., Gremer L., Tusche M., Flender D., Reinartz E., Hoyer W., Neudecker P., Willbold D., Heise H. 2021. Structural details of amyloid β oligomers in complex with human prion protein as revealed by solid-state MAS NMR spectroscopy. J. Biol. Chem. V. 296. P. 100499. https://doi.org/10.1016/j.jbc.2021.100499

  59. Konstantoulea K., Louros N., Rousseau F., Schymkowitz J. 2021. Heterotypic interactions in amyloid function and disease. FEBS J. V. 289. P. 2025. https://doi.org/10.1111/febs.15719

  60. Koopman M.B., Ferrari L., Rüdiger S.G.D. 2022. How do protein aggregates escape quality control in neurodegeneration? Trends Neurosci. V. 45. P. 257. https://doi.org/10.1016/j.tins.2022.01.006

  61. LaFerla F.M., Green K.N., Oddo S. 2007. Intracellular amyloid-beta in Alzheimer’s disease. Nat. Rev. Neurosci. V. 8. P. 499. https://doi.org/10.1038/nrn2168

  62. Lambert M.P., Velasco P.T., Chang L., Viola K.L., Fernandez S., Lacor P.N., Khuon D., Gong Y., Bigio E.H., Shaw P., De Felice F.G., Krafft G.A., Klein W.L. 2007. Monoclonal antibodies that target pathological assemblies of Abeta. J. Neurochem. V. 100. P. 23. https://doi.org/10.1111/j.1471-4159.2006.04157.x

  63. Li D., Liu C. 2022. Spatiotemporal dynamic regulation of membraneless organelles by chaperone networks. Trends Cell. Biol. V. 32. P. 1. https://doi.org/10.1016/j.tcb.2021.08.004

  64. Li F., Calingasan N.Y., Yu F., Mauck W.M., Toidze M., Almeida C.G., Takahashi R.H., Carlson G.A., Flint Beal M., Lin M.T., Gouras G.K. 2004. Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice. J. Neurochem. V. 89. P. 1308. https://doi.org/10.1111/j.1471-4159.2004.02455.x

  65. Liang C., Savinov S.N., Fejzo J., Eyles S.J., Chen J. 2019. Modulation of amyloid-β42 conformation by small molecules through nonspecific binding. J. Chem. Theory Comput. V. 15. P. 5169. https://doi.org/10.1021/acs.jctc.9b00599

  66. Limbocker R., Staats R., Chia S., Ruggeri F.S., Mannini B., Xu C.K., Perni M., Cascella R., Bigi A., Sasser L.R., Block N.R., Wright A.K., Kreiser R.P., Custy E.T., Meisl G. et al. 2021. Squalamine and its derivatives modulate the aggregation of amyloid-β and α-synuclein and suppress the toxicity of their oligomers. Front. Neurosci. V. 15. P. 680 026. https://doi.org/10.3389/fnins.2021.680026

  67. Lindersson E., Beedholm R., Højrup P., Moos T., Gai W., Hendil K.B., Jensen P.H. 2004. Proteasomal inhibition by alpha-synuclein filaments and oligomers. J. Biol. Chem. V. 279. P. 12924.

  68. Lorenzen N., Nielsen S.B., Yoshimura Y., Vad B.S., Andersen C.B., Betzer C., Kaspersen J.D., Christiansen G., Pedersen J.S., Jensen P.H., Mulder F.A., Otzen D.E. 2014. How epigallocatechin gallate can inhibit α-synuclein oligomer toxicity in vitro. J. Biol. Chem. V. 289. P. 21299. https://doi.org/10.1074/jbc.M114.554667

  69. Luth E.S., Stavrovskaya I.G., Bartels T., Kristal B.S., Selkoe D.J. 2014. Soluble, prefibrillar α-synuclein oligomers promote complex I-dependent, Ca2(+)-induced mitochondrial dysfunction. J. Biol. Chem. V. 289. P. 21490. https://doi.org/10.1074/jbc.M113.545749

  70. Macreadie I., Lotfi-Miri M., Mohotti S., Shapira D., Bennett L., Varghese J. 2008. Validation of folate in a convenient yeast assay suited for identification of inhibitors of Alzheimer’s amyloid-β aggregation. J. Alzheimers Dis. V. 15. P. 391. https://doi.org/10.3233/JAD-2008-15305

  71. Margulis B., Tsimokha A., Zubova S., Guzhova I. 2020. Molecular chaperones and proteolytic machineries regulate protein homeostasis in aging cells. Cells. V. 9. P. 1308. https://doi.org/10.3390/cells9051308

  72. Masliah E. 2001. Recent advances in the understanding of the role of synaptic proteins in Alzheimer’s disease and other neurodegenerative disorders. J. Alzheimers Dis. V. 3. P. 121. https://doi.org/10.3233/jad-2001-3117

  73. Mizuno H., Fujikake N., Wada K., Nagai Y. 2010. α-Synuclein transgenic Drosophila as a model of Parkinson’s disease and related synucleinopathies. Parkinsons Dis. V. 2011. P. 212 706. https://doi.org/10.4061/2011/212706

  74. Nevzglyadova O.V., Mikhailova E.V., Soidla T.R. 2022. Yeast red pigment, protein aggregates, and amyloidoses: a review. Cell Tiss. Res. V. 388. P. 211. https://doi.org/10.1007/s00441-022-03609-w

  75. Niewiadomska G., Niewiadomski W., Steczkowska M., Gasiorowska A. 2021. Tau oligomers neurotoxicity. Life (Basel). V. 11. P. 28. https://doi.org/10.3390/life11010028

  76. Nygaard H.B., van Dyck C.H., Strittmatter S.M. 2014. Fyn kinase inhibition as a novel therapy for Alzheimer’s disease. Alzheimers Res. Ther. V. 6. P. 8. https://doi.org/10.1186/alzrt238

  77. Opazo C., Huang X., Cherny R.A., Moir R.D., Roher A.E., White A.R., Cappai R., Masters C.L., Tanzi R.E., Inestrosa N.C., Bush A.I. 2002. Metalloenzyme-like activity of Alzheimer’s disease beta-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H(2)O(2). J. Biol. Chem. V. 277. P. 40302. https://doi.org/10.1074/jbc.M206428200

  78. Palhano F.L., Lee J., Grimster N.P., Kelly J.W. 2013. Toward the molecular mechanism(s) by which EGCG treatment remodels mature amyloid fibrils. J. Am. Chem. Soc. V. 135. P. 7503. https://doi.org/10.1021/ja3115696

  79. Paslawski W., Mysling S., Thomsen K., Jorgensen T.J., Otzen D.E. 2014. Co-existence of two different α-synuclein oligomers with different core structures determined by hydrogen/deuterium exchange mass spectrometry. Angew. Chem. Int. Ed. Engl. V. 53. P. 7560. https://doi.org/10.1002/anie.201400491

  80. Pena-Diaz S., Ventura S. 2022. One ring is sufficient to inhibit α-synuclein aggregation. Neural Regen. Res. V. 17. P. 508. https://doi.org/10.4103/1673-5374.320973

  81. Penke B., Bogár F., Paragi G., Gera J., Fülöp L. 2019. Key peptides and proteins in Alzheimer’s disease. Curr. Protein Pept. Sci. V. 20. P. 577. https://doi.org/10.2174/1389203720666190103123434

  82. Penke B., Szűcs M., Bogár F. 2020. Oligomerization and conformationalchange turn monomeric β-Amyloid and tau proteins toxic: their role in Alzheimer’s pathogenesis. Molecules. V. 25. P. 1659. https://doi.org/10.3390/molecules25071659

  83. Perni M., Flagmeier P., Limbocker R., Cascella R., Aprile F.A., Galvagnion C., Heller G.T., Meisl G., Chen S.W., Kumita J.R., Challa P.K., Kirkegaard J.B., Cohen S.I.A., Mannini B., Barbut D. et al. 2018. Multistep inhibition of α-synuclein aggregation and toxicity in vitro and in vivo by trodusquemine. ACS Chem. Biol. V. 13. P. 2308.

  84. https://doi.org/10.1021/acschembio.8b00466

  85. Perni M., van der Goot A., Limbocker R., van Ham T.J., Aprile F.A., Xu C.K., Flagmeier P., Thijssen K., Sormanni P., Fusco G., Chen S.W., Challa P.K., Kirkegaard J.B., Laine R.F., Ma K.Y. et al. 2021. Comparative studies in the A30P and A53T α-synuclein C. elegans strains to investigate the molecular origins of Parkinson’s disease. Front. Cell Dev. Biol. V. 9. P. 552549. https://doi.org/10.3389/fcell.2021.552549

  86. Rajasekhar K., Suresh S.N., Manjithaya R., Govindaraju T. 2015. Rationally designed peptidomimetic modulators of aβ toxicity in Alzheimer’s disease. Sci Rep. V. 30. P. 8139. https://doi.org/10.1038/srep08139

  87. Russo R., Borghi R., Markesbery W., Tabaton M., Piccini A. 2005. Neprylisin decreases uniformly in Alzheimer’s disease and in normal aging. FEBS Lett. V. 579. P. 6027. https://doi.org/10.1016/j.febslet.2005.09.054

  88. Sangkaew A., Kojornna T., Tanahashi R., Takagi H., Yompakdee C. 2022. A novel yeast-based screening system for potential compounds that can alleviate human α-synuclein toxicity. J. Appl. Microbiol. V. 132. P. 1409. https://doi.org/10.1111/jam.15256

  89. Santos J., Pallarès I., Ventura S. 2022. Is a cure for Parkinson’s disease hiding inside us? Trends Biochem. Sci. V. 19. P. S0968-0004(22)00025-1. https://doi.org/10.1016/j.tibs.2022.02.001

  90. Schepers J., Behl C. 2021. Lipid droplets and autophagy-links and regulations from yeast to humans. J. Cell Biochem. V. 122. P. 602. https://doi.org/10.1002/jcb.29889

  91. Scudamore O., Ciossek T. 2018. Increased oxidative stress exacerbates α-synuclein aggregation in vivo. J. Neuropathol. Exp. Neurol. V. 77. P. 443. https://doi.org/10.1093/jnen/nly024

  92. Silva J.L., Vieira T.C., Cordeiro Y., de Oliveira G.A.P. 2022. Nucleic acid actions on abnormal protein aggregation, phase transitions and phase separation. Curr. Opin. Struct. Biol. V. 73. P. 102346. https://doi.org/10.1016/j.sbi.2022.102346

  93. Simonsen A., Wollert T. 2022. Don’t forget to be picky – selective autophagy of protein aggregates in neurodegenerative diseases. Curr. Opin. Cell Biol. V. 75. P. 102064. https://doi.org/10.1016/j.ceb.2022.01.009

  94. Stefani M., Dobson C.M. 2003. Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution. J. Mol. Med. (Berl.). V. 81. P. 678. https://doi.org/10.1007/s00109-003-0464-5

  95. Stefanis L. 2012. α-Synuclein in Parkinson’s disease. Cold Spring Harb. Perspect. Med. V. 2. P. a009399. https://doi.org/10.1101/cshperspect.a009399

  96. Su L.J., Auluck P.K., Outeiro T.F., Yeger-Lotem E., Kritzer J.A., Tardiff D.F., Strathearn K.E., Liu F., Cao S., Hamamichi S., Hill K.J., Caldwell K.A., Bell G.W., Fraenkel E., Cooper A.A. et al. 2010. Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson’s disease models. Dis. Model. Mech. V. 3. P. 194. https://doi.org/10.1242/dmm.004267

  97. Subedi S., Sasidharan S., Nag N., Saudagar P., Tripathi T. 2022. Amyloid cross-seeding: mechanism, implication, and inhibition. Molecules. V. 27. P. 1776. https://doi.org/10.3390/molecules27061776

  98. Tang Y., Zhang D., Liu Y., Zhang Y., Zhou Y., Chang Y., Zheng B., Xu A., Zheng J. 2022a. A new strategy to reconcile amyloid cross-seeding and amyloid prevention in a binary system of α-synuclein fragmental peptide and hIAPP. Protein Science. V. 31. P. 485. https://doi.org/10.1002/pro.4247

  99. Tang Y., Zhang D., Zhang Y., Liu Y., Miller Y., Gong K., Zheng J. 2022b. Cross-seeding between Aβ and SEVI indicates a pathogenic link and gender difference between Alzheimer diseases and AIDS. Communications Biology. V. 5. P. 417. https://doi.org/10.1038/s42003-022-03343-7

  100. Tanguy E., Wang Q., Moine H., Vitale N. 2019. Phosphatidic acid: from pleiotropic functions to neuronal pathology. Front. Cell Neurosci. V. 13. P. 2. https://doi.org/10.3389/fncel.2019.00002

  101. Tardiff D.F., Jui N.T., Khurana V., Tambe M.A., Thompson M.L., Chung C.Y., Kamadurai H.B., Kim H.T., Lancaster A.K., Caldwell K.A., Caldwell G.A., Rochet J.C., Buchwald S.L., Lindquist S. 2013. Yeast reveal a druggable Rsp5/Nedd4 network that ameliorates α-synuclein toxicity in neurons. Science. V. 342. P. 979. https://doi.org/10.1126/science.1245321

  102. Tavanti F., Pedone A., Menziani M.C. 2020. Insights into the effect of curcumin and (–)-epigallocatechin-3-gallate on the aggregation of Aβ(1–40) monomers by means of molecular dynamics Int. J. Mol. Sci. V. 21. P. 5462. https://doi.org/10.3390/ijms21155462

  103. Tenreiro S., Munder M.C., Alberti S., Outeiro T.F. 2013. Harnessing the power of yeast to unravel the molecular basis of neurodegeneration. J. Neurochem. V. 127. P. 438. https://doi.org/10.1111/jnc.12271

  104. Thellung S., Corsaro A., Nizzari M., Barbieri F., Florio T. 2019. Autophagy activator drugs: anew opportunity in neuroprotection from misfolded protein toxicity. Int. J. Mol. Sci. V. 20. P. 901. https://doi.org/10.3390/ijms20040901

  105. Tuite M.F. 2019. Yeast models of neurodegenerative diseases. Prog. Mol. Biol. Transl. Sci. V. 168. P. 351. https://doi.org/10.1016/bs.pmbts.2019.07.001

  106. Vernon R.M., Chong P.A., Tsang B., Kim T.H., Bah A., Farber P., Lin H., Forman-Kay J.D. 2018. Pi-Pi contacts are an overlooked protein feature relevant to phase separation. Elife. V. 7. P. e31486. https://doi.org/10.7554/eLife.31486

  107. Villar-Piqué A., da Fonseca T.L., Sant’Anna R., Szegö É.M., Fonseca-Ornelas L., Pinho R., Carija A., Gerhardt E., Masaracchia C., Abad G.E., Rossetti G., Carloni P., Fernández C.O., Foguel D., Milosevic I. et al. 2016. Environmental and genetic factors support the dissociation between α-synuclein aggregation and toxicity. Proc. Natl. Acad. Sci. USA.V. 113. P. E6506. https://doi.org/10.1073/pnas.1606791113

  108. Vivoli Vega M., Cascella R., Chen S.W., Fusco G., De Simone A., Dobson C.M., Cecchi C., Chiti F. 2019. The toxicity of misfolded protein oligomers is independent of their secondary structure. ACS Chem. Biol. V. 14. P. 1593. https://doi.org/10.1021/acschembio.9b00324

  109. Volles M.J., Lee S.J., Rochet J.C., Shtilerman M.D., Ding T.T., Kessler J.C., Lansbury P.T. Jr. 2001. Vesicle permeabilization by protofibrillar alpha-synuclein: implications for the pathogenesis and treatment of Parkinson’s disease. Biochemistry. V. 40. P. 7812. https://doi.org/10.1021/bi0102398

  110. Wang Y., Westermark G.T. 2021. The amyloid forming peptide islet amyloid polypeptide and amyloid β interact at the molecular level. Int. J. Mol. Sci. V. 22. P. 11153. https://doi.org/10.3390/ijms222011153

  111. Wells C., Brennan S.E., Keon M., Ooi L. 2021. The role of amyloid oligomers in neurodegenerative pathologies. Int. J. Biol. Macromol. V. 181. P. 582. https://doi.org/10.1016/j.ijbiomac.2021.03.113

  112. Wells C., Brennan S.E., Keon M., Saksena N.K. 2019. Prionoid proteins in the pathogenesis of neurodegenerative diseases. Front. Mol. Neurosci. V. 12. P. 271. https://doi.org/10.3389/fnmol.2019.00271

  113. Wentink A., Nussbaum-Krammer C., Bukau B. 2019. Modulation of amyloid states by molecular chaperones. Cold Spring Harb. Perspect. Biol. V. 11. P. a033969. https://doi.org/10.1101/cshperspect.a033969

  114. Xue W.F., Hellewell A.L., Hewitt E.W., Radford S.E. 2010. Fibril fragmentation in amyloid assembly and cytotoxicity. Prion. V. 4. P. 20. https://doi.org/10.4161/pri.4.1.11378

  115. Youn K., Ho C., Jun M. 2022. Multifaceted neuroprotective effects of (-)-epigallocatechin-3-gallate (EGCG) in Alzheimer’s disease: an overview of pre-clinical studies focused on β-amyloid peptide. Food Sci. Human Wellness. V. 11. P. 483. https://doi.org/10.1016/j.fshw.2021.12.006

  116. Younan N.D., Chen K.F., Rose R.S., Crowther D.C., Viles J.H. 2018. Prion protein stabilizes amyloid-β (βA) oligomers and enhances Aβ neurotoxicity in a Drosophila model of Alzheimer’s disease. J. Biol. Chem. V. 293. P. 13090. https://doi.org/10.1074/jbc.RA118.003319

  117. Young L.M., Mahood R.A., Saunders J.C., Tu L.H., Raleigh D.P., Radford S.E., Ashcroft A.E. 2015. Insights into the consequences of co-polymerisation in the early stages of IAPP and Aβ peptide assembly from mass spectrometry. Analyst. V. 140. P. 6990. https://doi.org/10.1039/c5an00865d

  118. Zhang S., Liu Y.Q., Jia C., Lim Y.J., Feng G., Xu E., Long H., Kimura Y., Tao Y., Zhao C., Wang C., Liu Z., Hu J.J., Ma M.R., Liu Z. et al. 2021. Mechanistic basis for receptor-mediated pathological α-synuclein fibril cell-to-cell transmission in Parkinson’s disease. Proc. Natl. Acad. Sci. USA. V. 118. P. e2011196118. https://doi.org/10.1073/pnas.2011196118

  119. Zhang Y., Zhang M., Liu Y., Zhang D., Tang Y., Ren B., Zheng J. 2021. Dual amyloid cross-seeding reveals steric zipper-facilitated fibrillization and pathological links between protein misfolding diseases. J. Mat. Chem B. V. 9. P. 3300. https://doi.org/10.1039/D0TB0295K

  120. Zhang Y., Zhao Y., Zhang L., Yu W., Wang Y., Chang W. 2019. Cellular prion protein as a receptor of toxic amyloid-β 42 oligomers is important for Alzheimer’s disease. Front Cell Neurosci. V. 13. P. 339. https://doi.org/10.3389/fncel.2019.00339

Дополнительные материалы отсутствуют.

Инструменты

следующая статья выпуска предыдущая статья выпуска содержание выпуска

Цитология

Архивы выпусков Информация о журнале Отправить рукопись в журнал