SpringerLink
Log in

Molecular Mechanisms Underlying Alzheimer’s and Parkinson’s Disease and the Possibility of Their Neutralization

  • Published:
Cell and Tissue Biology Aims and scope Submit manuscript

Abstract

Under the influence of external and internal factors, various changed proteins inevitably arise in cells. With age, the activity of chaperones and other components of cellular control over protein quality decreases. This is accompanied by the accumulation of misfolded proteins with altered conformations. The most dramatic event for the cell is the transformation of an active soluble protein into an amyloid insoluble and inactive state. It is believed that this change in protein conformation underlies the process of neurodegeneration. Although this process is being intensively studied, many details of neurodegeneration remain unclear. In this review, we present the currently most accepted molecular mechanisms of the pathogenesis of the most common neurodegenerative diseases, Alzheimer’s and Parkinson’s. They include sequential reactions β-amyloid and α-synuclein with membrane receptors and are modulated by phase separation and cross-seeding with other cellular prions. Particular attention is paid to natural polyfunctional compounds as the most therapeutically promising.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

Similar content being viewed by others

REFERENCES

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Banerjee, D. and Sanyal, S., Protein folding activity of the ribosome (PFAR)—a target for antiprion compounds, Viruses, 2014, vol. 6, p. 3907. https://doi.org/10.3390/v6103907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Barbitoff, Y.A., Matveenko, A.G., Moskalenko, S.E., Zemlyanko, O.M., Newnam, G.P., Patel, A., Chernova, T.A., Chernoff, Y.O., and Zhouravleva, G.A., 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., 2017, vol. 105, p. 242. https://doi.org/10.1111/mmi.13697

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

  12. 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., and Hyman, B.T., Enhanced tau aggregation in the presence of amyloid β, Am. J. Pathol., 2017, vol. 187, p. 1601. https://doi.org/10.1016/j.ajpath.2017.03.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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., and Newsholme, P., Amylin and beta amyloid proteins interact to form amorphous heterocomplexes with enhanced toxicity in neuronal cells, Sci. Rep., 2020, vol. 10, p. 10356. https://doi.org/10.1038/s41598-020-66602-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 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., and Voisset, C., Protein folding activity of the ribosome is involved in yeast prion propagation, Sci. Rep., 2016, vol. 6, p. 32117. https://doi.org/10.1038/srep32117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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., and Linse, S., A molecular chaperone breaks the catalytic cycle that generates toxic Aβ-oligomers, Nat. Struct. Mol. Biol., 2015, vol. 22, p. 207. https://doi.org/10.1038/nsmb.2971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  28. Doody, R.S., Gavrilova, S.I., Sano, M., Thomas, R.G., Aisen, P.S., Bachurin, S.O., Seely, L., Hung, D., and Dimebon, I., 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, 2008, vol. 372, p. 207. https://doi.org/10.1016/S0140-6736(08)61074-0

    Article  CAS  PubMed  Google Scholar 

  29. 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., and Colin, M., Ectosomes: a new mechanism for non-exosomal secretion of Tau protein, PLoS One, 2014, vol. 9, p. e100760. https://doi.org/10.1371/journal.pone.0100760

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Franić, D., Zubčić, K., and Boban, M., Nuclear ubiquitin-proteasome pathways in proteostasis maintenance, Biomolecules, 2021, vol. 4, p. 54. https://doi.org/10.3390/biom11010054

    Article  CAS  Google Scholar 

  36. 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., and De Simone, A., Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers, Science, 2017, vol. 358, p. 1440. https://doi.org/10.1126/science.aan6160

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  38. Gomes, L.M.F., Bataglioli, J.C., and Storr, T.,Metal complexes that bind to the amyloid-β peptide of relevance to Alzheimer’s disease, Coordinat. Chem. Rev., 2020, vol. 412, p. 213255. https://doi.org/10.1016/j.ccr.2020.213255

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  40. 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., and Vendruscolo, M., Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes, Nat. Chem., 2018, vol. 10, p. 673. https://doi.org/10.1038/s41557-018-0031-x

    Article  CAS  PubMed  Google Scholar 

  41. Hachiya N., Fułek 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

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

    Article  CAS  PubMed  Google Scholar 

  43. Hardenberg,M., Horvath, A., Ambrus, V., Fuxreiter, M., and Vendruscolo, M.,Widespread occurrence of the droplet state of proteins in the human proteome, Proc. Natl. Acad. Sci. U. S. A., 2020, vol. 117, p. 33254. https://doi.org/10.1073/pnas.2007670117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. 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., and Vendruscolo, M., Observation of an α-synuclein liquid droplet state and its maturation into Lewy body-like assemblies, J. Mol. Cell Biol., 2021, vol. 13, p. 282. https://doi.org/10.1093/jmcb/mjaa075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hashimoto, M. and Masliah, E., Alpha-synuclein in Lewy body disease and Alzheimer’s disease, Brain Pathol., 1999, vol. 9, p. 707. https://doi.org/10.1111/j.1750-3639.1999.tb00552.x

    Article  CAS  PubMed  Google Scholar 

  46. Hevroni, B.L., Major, D.T., Dixit, M., Mhashal, A.R., Das, S., and Fischer, B., 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, Org. Biomol. Chem., 2016, vol. 14, p. 4640. http://goi.org/10/1039/C6OB00613B

    Article  CAS  PubMed  Google Scholar 

  47. 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., and Ikenaka, K., Two-step screening method to identify α-synuclein aggregation inhibitors for Parkinson’s disease, Sci. Rep., 2022, vol. 12, p. 351. https://doi.org/10.1038/s41598-021-04131-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  52. 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., and Johnson, K.A., Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals, Nat.Neurosci., 2018, vol. 21, p. 424. https://doi.org/10.1038/s41593-018-0070-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  61. 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., and Klein, W.L., Monoclonal antibodies that target pathological assemblies of Abeta, J. Neurochem., 2007, vol. 100, p. 23. https://doi.org/10.1111/j.1471-4159.2006.04157.x

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  63. 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., and Gouras, G.K., Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice, J. Neurochem., 2004, vol. 89, p. 1308. https://doi.org/10.1111/j.1471-4159.2004.02455.x

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. 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., Squalamine and its derivatives modulate the aggregation of amyloid-β and α-synuclein and suppress the toxicity of their oligomers, Front. Neurosci., 2021, vol. 15, p. 680026. https://doi.org/10.3389/fnins.2021.680026

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  74. Niewiadomska, G., Niewiadomski, W., Steczkowska, M., and Gasiorowska, A., Tau oligomers neurotoxicity, Life (Basel), 2021, vol. 11, p. 28. https://doi.org/10.3390/life11010028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  76. 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., and Bush, A.I., 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., 2002, vol. 277, p. 40302. https://doi.org/10.1074/jbc.M206428200

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. 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., Multistep inhibition of α-synuclein aggregation and toxicity in vitro and in vivo by trodusquemine, ACS Chem. Biol., 2018, vol. 13, p. 2308. https://doi.org/10.1021/acschembio.8b00466

    Article  CAS  PubMed  Google Scholar 

  83. 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., 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., 2021, vol. 9, p. 552549. https://doi.org/10.3389/fcell.2021.552549

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  93. Stefanis, L., α-Synuclein in Parkinson's disease, Cold Spring Harb. Perspect. Med., 2012, vol. 2, p. a009399. https://doi.org/10.1101/cshperspect.a009399

  94. 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., Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson’s disease models, Dis. Model. Mech., 2010, vol. 3, p. 194. https://doi.org/10.1242/dmm.004267

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. 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., and Lindquist, S., Yeast reveal a druggable Rsp5/Nedd4 network that ameliorates α-synuclein toxicity in neurons, Science, 2013, vol. 342, p. 979. https://doi.org/10.1126/science.1245321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Tavanti, F., Pedone, A., and Menziani, M.C.,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., 2020, vol. 21, p. 5462. https://doi.org/10.3390/ijms21155462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  102. Thellung, S., Corsaro, A., Nizzari, M., Barbieri, F., and Florio, T.,Autophagy activator drugs: a new opportunity in neuroprotection from misfolded protein toxicity, Int. J. Mol. Sci., 2019, vol. 20, p. 901. https://doi.org/10.3390/ijms20040901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Tuite, M.F., Yeast models of neurodegenerative diseases, Prog. Mol. Biol. Transl. Sci., 2019, vol. 168, p. 351. https://doi.org/10.1016/bs.pmbts.2019.07.001

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  105. 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., Environmental and genetic factors support the dissociation between α-synuclein aggregation and toxicity, Proc. Natl. Acad. Sci. U. S. A., 2016, vol. 113, p. E6506. https://doi.org/10.1073/pnas.1606791113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Youn, K., Ho, C., and Jun, M.,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. Hum. Wellness, 2022, vol. 11, p. 483. https://doi.org/10.1016/j.fshw.2021.12.006

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. 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., Mechanistic basis for receptor-mediated pathological α-synuclein fibril cell-to-cell transmission in Parkinson’s disease, Proc. Natl. Acad. Sci. U. S. A., 2021a, vol. 118, p. e2011196118. https://doi.org/10.1073/pnas.2011196118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  119. Zubova, S.G., The diversity of autophagy and its controversial role in biological processes, Tsitologiya, 2019, vol. 61, no. 12, p. 941. https://doi.org/10.1134/S0041377119120095

    Article  Google Scholar 

Download references

Funding

The work was carried out at the expense of the budgetary funds of the Institute of Cytology of the Russian Academy of Sciences, subject no. AAAA-A17-117032350034-7.

Author information

Authors and Affiliations

  1. Institute of Cytology, Russian Academy of Sciences, 194064, St. Petersburg, Russia

    O. V. Nevzglyadova, E. V. Mikhailova & T. R. Soidla

Authors
  1. O. V. Nevzglyadova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. V. Mikhailova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. R. Soidla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O. V. Nevzglyadova.

Ethics declarations

The authors declare that they have no conflicts of interest.

The work did not include experiments involving animals or human beings.

Additional information

Publisher’s Note.

Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abbreviations: βA—β-amyloid; AS—α-synuclein; ROS—reactive oxygen species; AD—Alzheimer’s disease; PD—Parkinson’s disease; RP—red yeast pigment; NMO—nonmembrane organelle; TAG—triacylglycerol; ES—ester of sterol; EGCG—epigalocatechin gallate; calcein–AM—calcein acetoxymethyl.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nevzglyadova, O.V., Mikhailova, E.V. & Soidla, T.R. Molecular Mechanisms Underlying Alzheimer’s and Parkinson’s Disease and the Possibility of Their Neutralization. Cell Tiss. Biol. 17, 593–607 (2023). https://doi.org/10.1134/S1990519X23060093

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990519X23060093

Keywords:

Search

Navigation