β-synuclein regulates the phase transitions and amyloid conversion of α-synuclein.
alpha-Synuclein
/ metabolism
Caenorhabditis elegans
/ metabolism
Animals
Humans
beta-Synuclein
/ metabolism
Parkinson Disease
/ metabolism
Amyloid
/ metabolism
Phase Transition
Mutation
Lewy Body Disease
/ metabolism
Caenorhabditis elegans Proteins
/ metabolism
Presynaptic Terminals
/ metabolism
Longevity
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 Oct 2024
09 Oct 2024
Historique:
received:
13
05
2024
accepted:
30
09
2024
medline:
10
10
2024
pubmed:
10
10
2024
entrez:
9
10
2024
Statut:
epublish
Résumé
Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated β-synuclein mutations lose these capacities. Exogenous β-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated β-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/β-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and β-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.
Identifiants
pubmed: 39384788
doi: 10.1038/s41467-024-53086-8
pii: 10.1038/s41467-024-53086-8
doi:
Substances chimiques
alpha-Synuclein
0
beta-Synuclein
0
Amyloid
0
Caenorhabditis elegans Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8748Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 31971066
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82273838
Organisme : Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation)
ID : 2021CFA004
Informations de copyright
© 2024. The Author(s).
Références
Shin, Y. & Brangwynne, C. P. Liquid phase condensation in cell physiology and disease. Science 357, eaaf4382 (2017).
pubmed: 28935776
doi: 10.1126/science.aaf4382
Agarwal, A., Arora, L., Rai, S. K., Avni, A. & Mukhopadhyay, S. Spatiotemporal modulations in heterotypic condensates of prion and α-synuclein control phase transitions and amyloid conversion. Nat. Commun. 13, 1154 (2022).
pubmed: 35241680
pmcid: 8894376
doi: 10.1038/s41467-022-28797-5
Chakraborty, P. & Zweckstetter, M. Role of aberrant phase separation in pathological protein aggregation. Curr. Opin. Struct. Biol. 82, 102678 (2023).
pubmed: 37604044
doi: 10.1016/j.sbi.2023.102678
Castillo-Barnes, D. et al. Nonlinear weighting ensemble learning model to diagnose Parkinson’s disease using multimodal data. Int J. Neural Syst. 33, 2350041 (2023).
pubmed: 37470777
doi: 10.1142/S0129065723500417
Rey, N. L. et al. Widespread transneuronal propagation of α-synucleinopathy triggered in olfactory bulb mimics prodromal Parkinson’s disease. J. Exp. Med. 213, 1759–1778 (2016).
pubmed: 27503075
pmcid: 4995088
doi: 10.1084/jem.20160368
Ray, S. et al. α-Synuclein aggregation nucleates through liquid-liquid phase separation. Nat. Chem. 12, 705–716 (2020).
pubmed: 32514159
doi: 10.1038/s41557-020-0465-9
Barba, L. et al. Alpha and beta synucleins: from pathophysiology to clinical application as biomarkers. Mov. Disord. 37, 669–683 (2022).
pubmed: 35122299
pmcid: 9303453
doi: 10.1002/mds.28941
Perni, M. et al. A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity. Proc. Natl Acad. Sci. USA 114, E1009–E1017 (2017).
pubmed: 28096355
pmcid: 5307473
doi: 10.1073/pnas.1610586114
Ray, S. et al. Mass photometric detection and quantification of nanoscale α-synuclein phase separation. Nat. Chem. 15, 1306–1316 (2023).
pubmed: 37337111
doi: 10.1038/s41557-023-01244-8
Wilhelm, B. G. et al. Composition of isolated synaptic boutons reveals the amounts of vesicle trafficking proteins. Science 344, 1023–1028 (2014).
pubmed: 24876496
doi: 10.1126/science.1252884
Jain, M. K., Singh, P., Roy, S. & Bhat, R. Comparative analysis of the conformation, aggregation, interaction, and fibril morphologies of human α-, β-, and γ-synuclein proteins. Biochemistry 57, 3830–3848 (2018).
pubmed: 29851342
doi: 10.1021/acs.biochem.8b00343
Hoffman-Zacharska, D. et al. Novel A18T and pA29S substitutions in α-synuclein may be associated with sporadic Parkinson’s disease. Parkinsonism Relat. Disord. 19, 1057–1060 (2013).
pubmed: 23916651
pmcid: 4055791
doi: 10.1016/j.parkreldis.2013.07.011
Joshi, N., Sarhadi, T. R., Raveendran, A. & Nagotu, S. Sporadic SNCA mutations A18T and A29S exhibit variable effects on protein aggregation, cell viability and oxidative stress. Mol. Biol. Rep. 50, 5547–5556 (2023).
pubmed: 37155014
doi: 10.1007/s11033-023-08457-7
Guan, Y. et al. Pathogenic mutations differentially regulate cell-to-cell transmission of α-synuclein. Front Cell Neurosci. 14, 159 (2020).
pubmed: 32595456
pmcid: 7303300
doi: 10.3389/fncel.2020.00159
Kumar, S. et al. Role of sporadic Parkinson disease associated mutations A18T and A29S in enhanced α-synuclein fibrillation and cytotoxicity. ACS Chem. Neurosci. 9, 230–240 (2018).
pubmed: 28841377
doi: 10.1021/acschemneuro.6b00430
Ji, K. et al. Inhibition effects of tanshinone on the aggregation of α-synuclein. Food Funct. 7, 409–416 (2016).
pubmed: 26456030
doi: 10.1039/C5FO00664C
Li, Y. et al. Copper and iron ions accelerate the prion-like propagation of α-synuclein: a vicious cycle in Parkinson’s disease. Int J. Biol. Macromol. 163, 562–573 (2020).
pubmed: 32629061
doi: 10.1016/j.ijbiomac.2020.06.274
Ma, L. et al. C-terminal truncation exacerbates the aggregation and cytotoxicity of α-Synuclein: a vicious cycle in Parkinson’s disease. Biochim. Biophys. Acta Mol. Basis Dis. 1864, 3714–3725 (2018).
pubmed: 30290273
doi: 10.1016/j.bbadis.2018.10.003
Hashimoto, M. et al. Beta-synuclein regulates Akt activity in neuronal cells. A possible mechanism for neuroprotection in Parkinson’s disease. J. Biol. Chem. 279, 23622–23629 (2004).
pubmed: 15026413
doi: 10.1074/jbc.M313784200
Park, J. Y. & Lansbury, P. T. Jr Beta-synuclein inhibits formation of alpha-synuclein protofibrils: a possible therapeutic strategy against Parkinson’s disease. Biochemistry 42, 3696–3700 (2003).
pubmed: 12667059
doi: 10.1021/bi020604a
Hayashi, J. & Carver, J. A. β-synuclein: an enigmatic protein with diverse functionality. Biomolecules 12, 142 (2022).
pubmed: 35053291
pmcid: 8773819
doi: 10.3390/biom12010142
Ohtake, H. et al. Beta-synuclein gene alterations in dementia with Lewy bodies. Neurology 63, 805–811 (2004).
pubmed: 15365127
doi: 10.1212/01.WNL.0000139870.14385.3C
Beyer, K. et al. New brain-specific beta-synuclein isoforms show expression ratio changes in Lewy body diseases. Neurogenetics 13, 61–72 (2012).
pubmed: 22205345
doi: 10.1007/s10048-011-0311-8
Janowska, M. K., Wu, K. P. & Baum, J. Unveiling transient protein-protein interactions that modulate inhibition of alpha-synuclein aggregation by beta-synuclein, a pre-synaptic protein that co-localizes with alpha-synuclein. Sci. Rep. 5, 15164 (2015).
pubmed: 26477939
pmcid: 4609965
doi: 10.1038/srep15164
Molliex, A. et al. Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization. Cell 163, 123–133 (2015).
pubmed: 26406374
pmcid: 5149108
doi: 10.1016/j.cell.2015.09.015
Rai, S. K., Khanna, R., Avni, A. & Mukhopadhyay, S. Heterotypic electrostatic interactions control complex phase separation of tau and prion into multiphasic condensates and co-aggregates. Proc. Natl Acad. Sci. USA 120, e2216338120 (2023).
pubmed: 36595668
pmcid: 9986828
doi: 10.1073/pnas.2216338120
Hatos, A., Tosatto, S. C. E., Vendruscolo, M. & Fuxreiter, M. FuzDrop on AlphaFold: visualizing the sequence-dependent propensity of liquid-liquid phase separation and aggregation of proteins. Nucleic Acids Res. 50, W337–W344 (2022).
pubmed: 35610022
pmcid: 9252777
doi: 10.1093/nar/gkac386
Gao, Y., Li, X., Li, P. & Lin, Y. A brief guideline for studies of phase-separated biomolecular condensates. Nat. Chem. Biol. 18, 1307–1318 (2022).
pubmed: 36400991
doi: 10.1038/s41589-022-01204-2
Zeng, M. et al. Phase transition in postsynaptic densities underlies formation of synaptic complexes and synaptic plasticity. Cell 166, 1163–1175.e12 (2016).
pubmed: 27565345
pmcid: 5564291
doi: 10.1016/j.cell.2016.07.008
Babinchak, W. M. et al. Small molecules as potent biphasic modulators of protein liquid-liquid phase separation. Nat. Commun. 11, 5574 (2020).
pubmed: 33149109
pmcid: 7643064
doi: 10.1038/s41467-020-19211-z
Dao, T. P. et al. Ubiquitin modulates liquid-liquid phase separation of UBQLN2 via disruption of multivalent interactions. Mol. Cell 69, 965–978.e6 (2018).
pubmed: 29526694
pmcid: 6181577
doi: 10.1016/j.molcel.2018.02.004
Gracia, P. et al. Molecular mechanism for the synchronized electrostatic coacervation and co-aggregation of alpha-synuclein and tau. Nat. Commun. 13, 4586 (2022).
pubmed: 35933508
pmcid: 9357037
doi: 10.1038/s41467-022-32350-9
Agudo-Canalejo, J. et al. Wetting regulates autophagy of phase-separated compartments and the cytosol. Nature 591, 142–146 (2021).
pubmed: 33473217
doi: 10.1038/s41586-020-2992-3
Piroska, L. et al. α-Synuclein liquid condensates fuel fibrillar α-synuclein growth. Sci. Adv. 9, eadg5663 (2023).
pubmed: 37585526
pmcid: 10431715
doi: 10.1126/sciadv.adg5663
Day, J. O. & Mullin, S. The genetics of Parkinson’s disease and implications for clinical practice. Genes 12, 1006 (2021).
pubmed: 34208795
pmcid: 8304082
doi: 10.3390/genes12071006
Psol, M. et al. Dementia with Lewy bodies-associated ß-synuclein mutations V70M and P123H cause mutation-specific neuropathological lesions. Hum. Mol. Genet 30, 247–264 (2021).
pubmed: 33760043
doi: 10.1093/hmg/ddab036
Ma, L. et al. Caenorhabditis elegans as a model system for target identification and drug screening against neurodegenerative diseases. Eur. J. Pharm. 819, 169–180 (2018).
doi: 10.1016/j.ejphar.2017.11.051
Huang, X. et al. Human amyloid beta and α-synuclein co-expression in neurons impair behavior and recapitulate features for Lewy body dementia in Caenorhabditis elegans. Biochim. Biophys. Acta Mol. Basis Dis. 1867, 166203 (2021).
pubmed: 34146705
doi: 10.1016/j.bbadis.2021.166203
Quilty, M. C., Gai, W. P., Pountney, D. L., West, A. K. & Vickers, J. C. Localization of alpha-, beta-, and gamma-synuclein during neuronal development and alterations associated with the neuronal response to axonal trauma. Exp. Neurol. 182, 195–207 (2003).
pubmed: 12821390
doi: 10.1016/S0014-4886(03)00108-0
Maroteaux, L., Campanelli, J. T. & Scheller, R. H. Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J. Neurosci. 8, 2804–2815 (1988).
pubmed: 3411354
pmcid: 6569395
doi: 10.1523/JNEUROSCI.08-08-02804.1988
Hashimoto, M., Rockenstein, E., Mante, M., Mallory, M. & Masliah, E. β-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-Parkinsonian factor. Neuron 32, 213–223 (2001).
pubmed: 11683992
doi: 10.1016/S0896-6273(01)00462-7
Baba, M. et al. Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies. Am. J. Pathol. 152, 879–884 (1998).
pubmed: 9546347
pmcid: 1858234
Beyer, K. et al. The decrease of β-synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies. Brain 133, 3724–3733 (2010).
pubmed: 20959308
doi: 10.1093/brain/awq275
Gao, C. et al. Hyperosmotic-stress-induced liquid-liquid phase separation of ALS-related proteins in the nucleus. Cell Rep. 40, 111086 (2022).
pubmed: 35858576
doi: 10.1016/j.celrep.2022.111086
Williams, J. K. et al. Multi-pronged interactions underlie inhibition of α-synuclein aggregation by β-synuclein. J. Mol. Biol. 430, 2360–2371 (2018).
pubmed: 29782835
pmcid: 6100766
doi: 10.1016/j.jmb.2018.05.024
Beyer, K., Ispierto, L., Latorre, P., Tolosa, E. & Ariza, A. Alpha- and beta-synuclein expression in Parkinson disease with and without dementia. J. Neurol. Sci. 310, 112–117 (2011).
pubmed: 21683963
doi: 10.1016/j.jns.2011.05.049
Yang, X., Williams, J. K., Yan, R., Mouradian, M. M. & Baum, J. Increased dynamics of α-synuclein fibrils by β-synuclein leads to reduced seeding and cytotoxicity. Sci. Rep. 9, 17579 (2019).
pubmed: 31772376
pmcid: 6879756
doi: 10.1038/s41598-019-54063-8
Mukherjee, S. et al. Liquid-liquid phase separation of α-synuclein: a new mechanistic insight for α-synuclein aggregation associated with Parkinson’s disease pathogenesis. J. Mol. Biol. 435, 167713 (2023).
pubmed: 35787838
doi: 10.1016/j.jmb.2022.167713
Gasset-Rosa, F. et al. Cytoplasmic TDP-43 de-mixing independent of stress granules drives inhibition of nuclear import, loss of nuclear TDP-43, and cell death. Neuron 102, 339–357.e7 (2019).
pubmed: 30853299
pmcid: 6548321
doi: 10.1016/j.neuron.2019.02.038
Liu, Y. Q. et al. 14-3-3ζ participates in the phase separation of phosphorylated and glycated tau and modulates the physiological and pathological functions of tau. ACS Chem. Neurosci. 14, 1220–1225 (2023).
pubmed: 36939323
doi: 10.1021/acschemneuro.3c00034
Leitao, A., Bhumkar, A., Hunter, D. J. B., Gambin, Y. & Sierecki, E. Unveiling a selective mechanism for the inhibition of α-synuclein aggregation by β-synuclein. Int J. Mol. Sci. 19, 334 (2018).
pubmed: 29364143
pmcid: 5855556
doi: 10.3390/ijms19020334
Bonner, L. T. et al. Familial dementia with Lewy bodies with an atypical clinical presentation. J. Geriatr. Psychiatry Neurol. 16, 59–64 (2003).
pubmed: 12641375
pmcid: 1482838
doi: 10.1177/0891988702250585
Janowska, M. K. & Baum, J. The loss of inhibitory C-terminal conformations in disease associated P123H β-synuclein. Protein Sci. 25, 286–294 (2016).
pubmed: 26332674
doi: 10.1002/pro.2798
Grossman, M. et al. Frontotemporal lobar degeneration. Nat. Rev. Dis. Prim. 9, 40 (2023).
pubmed: 37563165
doi: 10.1038/s41572-023-00447-0
Shenouda, M., Xiao, S., MacNair, L., Lau, A. & Robertson, J. A C-terminally truncated TDP-43 splice isoform exhibits neuronal specific cytoplasmic aggregation and contributes to TDP-43 pathology in ALS. Front. Neurosci. 16, 868556 (2022).
pubmed: 35801182
pmcid: 9253772
doi: 10.3389/fnins.2022.868556
Weskamp, K. et al. Shortened TDP43 isoforms upregulated by neuronal hyperactivity drive TDP43 pathology in ALS. J. Clin. Invest 130, 1139–1155 (2020).
pubmed: 31714900
pmcid: 7269575
doi: 10.1172/JCI130988
LeWitt, P. A. Levodopa therapy for Parkinson’s disease: pharmacokinetics and pharmacodynamics. Mov. Disord. 30, 64–72 (2015).
pubmed: 25449210
doi: 10.1002/mds.26082
Nonnekes, J. et al. Unmasking levodopa resistance in Parkinson’s disease. Mov. Disord. 31, 1602–1609 (2016).
pubmed: 27430479
doi: 10.1002/mds.26712
Pagano, G. et al. Trial of prasinezumab in early-stage Parkinson’s disease. N. Engl. J. Med. 387, 421–432 (2022).
pubmed: 35921451
doi: 10.1056/NEJMoa2202867
Lang, A. E. et al. Trial of cinpanemab in early Parkinson’s disease. N. Engl. J. Med. 387, 408–420 (2022).
pubmed: 35921450
doi: 10.1056/NEJMoa2203395
Freskgård, P. O. & Urich, E. Antibody therapies in CNS diseases. Neuropharmacology 120, 38–55 (2017).
pubmed: 26972827
doi: 10.1016/j.neuropharm.2016.03.014
Pardridge, W. M. The blood-brain barrier and neurotherapeutics. NeuroRx 2, 1–2 (2005).
pubmed: 15717052
pmcid: 539315
doi: 10.1602/neurorx.2.1.1
Khare, S. D., Chinchilla, P. & Baum, J. Multifaceted interactions mediated by intrinsically disordered regions play key roles in alpha synuclein aggregation. Curr. Opin. Struct. Biol. 80, 102579 (2023).
pubmed: 37060757
pmcid: 10910670
doi: 10.1016/j.sbi.2023.102579
Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18, 285–298 (2017).
pubmed: 28225081
pmcid: 7434221
doi: 10.1038/nrm.2017.7
Stiernagle, T. Maintenance of C. elegans. WormBook. 1–11 (2006).
Berkowitz, L. A., Knight, A. L., Caldwell, G. A. & Caldwell, K. A. Generation of stable transgenic C. elegans using microinjection. J. Vis. Exp. 15, 833 (2008).
Ma, L. et al. Modelling Parkinson’s disease in C. elegans: strengths and limitations. Curr. Pharm. Des. 28, 3033–3048 (2022).
pubmed: 36111767
doi: 10.2174/1381612828666220915103502
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
pubmed: 34265844
pmcid: 8371605
doi: 10.1038/s41586-021-03819-2
Huang, L. et al. Inhibitory effect of leonurine on the formation of advanced glycation end products. Food Funct. 6, 584–589 (2015).
pubmed: 25518982
doi: 10.1039/C4FO00960F
Yang, C. et al. Kidney injury molecule-1 is a potential receptor for SARS-CoV-2. J. Mol. Cell Biol. 13, 185–196 (2021).
pubmed: 33493263
pmcid: 7928767
doi: 10.1093/jmcb/mjab003
Xu, B. et al. Manganese promotes α-synuclein amyloid aggregation through the induction of protein phase transition. J. Biol. Chem. 298, 101469 (2022).
pubmed: 34871547
doi: 10.1016/j.jbc.2021.101469
Jadavi, S. et al. Fluorescence labeling methods influence the aggregation process of α-syn in vitro differently. Nanoscale 15, 8270–8277 (2023).
pubmed: 37073868
doi: 10.1039/D2NR05487F
Dai, B. et al. Myricetin slows liquid-liquid phase separation of Tau and activates ATG5-dependent autophagy to suppress Tau toxicity. J. Biol. Chem. 297, 101222 (2021).
pubmed: 34560101
pmcid: 8551527
doi: 10.1016/j.jbc.2021.101222
Klein, I. A. et al. Partitioning of cancer therapeutics in nuclear condensates. Science 368, 1386–1392 (2020).
pubmed: 32554597
pmcid: 7735713
doi: 10.1126/science.aaz4427
Benjamin, C. E. et al. Using FRET to measure the time it takes for a cell to destroy a virus. Nanoscale 12, 9124–9132 (2020).
pubmed: 32292962
doi: 10.1039/C9NR09816J
Song, S., Hanson, M. J., Liu, B. F., Chylack, L. T. & Liang, J. J. Protein-protein interactions between lens vimentin and alphaB-crystallin using FRET acceptor photobleaching. Mol. Vis. 14, 1282–1287 (2008).
pubmed: 18618007
pmcid: 2447818
Eckenstaler, R. & Benndorf, R. A. A combined acceptor photobleaching and donor fluorescence lifetime imaging microscopy approach to analyze multi-protein interactions in living cells. Front. Mol. Biosci. 8, 635548 (2021).
pubmed: 34055873
pmcid: 8160235
doi: 10.3389/fmolb.2021.635548
Wang, Z., Zhang, G. & Zhang, H. Protocol for analyzing protein liquid–liquid phase separation. Biophys. Rep. 5, 1–9 (2019).
doi: 10.1007/s41048-018-0078-7
Gong, H. et al. Effects of several quinones on insulin aggregation. Sci. Rep. 4, 5648 (2014).
pubmed: 25008537
pmcid: 4090620
doi: 10.1038/srep05648
Li, Y. et al. The effect of exposing a critical hydrophobic patch on amyloidogenicity and fibril structure of insulin. Biochem. Biophys. Res. Commun. 440, 56–61 (2013).
pubmed: 24041697
doi: 10.1016/j.bbrc.2013.09.032
Xu, B., Mo, X., Chen, J., Yu, H. & Liu, Y. Myricetin inhibits α-synuclein amyloid aggregation by delaying the liquid-to-solid phase transition. Chembiochem 23, e202200216 (2022).
pubmed: 35657723
doi: 10.1002/cbic.202200216
Ma, L. et al. A systematic screening of traditional Chinese medicine identifies two novel inhibitors against the cytotoxic aggregation of amyloid beta. Front. Pharm. 12, 637766 (2021).
doi: 10.3389/fphar.2021.637766
Cheng, B. et al. Salvianolic acid B inhibits the amyloid formation of human islet amyloid polypeptide and protects pancreatic beta-cells against cytotoxicity. Proteins 81, 613–621 (2013).
pubmed: 23180621
doi: 10.1002/prot.24216
Guo, C. et al. Inhibitory effects of magnolol and honokiol on human calcitonin aggregation. Sci. Rep. 5, 13556 (2015).
pubmed: 26324190
pmcid: 4555095
doi: 10.1038/srep13556
Ma, L. et al. Glycated insulin exacerbates the cytotoxicity of human islet amyloid polypeptides: a vicious cycle in type 2 diabetes. ACS Chem. Biol. 14, 486–496 (2019).
pubmed: 30715843
doi: 10.1021/acschembio.8b01128
Avni, A., Joshi, A., Walimbe, A., Pattanashetty, S. G. & Mukhopadhyay, S. Single-droplet surface-enhanced Raman scattering decodes the molecular determinants of liquid-liquid phase separation. Nat. Commun. 13, 4378 (2022).
pubmed: 35902591
pmcid: 9334365
doi: 10.1038/s41467-022-32143-0
Yang, C. et al. A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury. Nat. Commun. 14, 4261 (2023).
pubmed: 37460623
pmcid: 10352345
doi: 10.1038/s41467-023-40036-z
Cheng, B. et al. Coffee components inhibit amyloid formation of human islet amyloid polypeptide in vitro: possible link between coffee consumption and diabetes mellitus. J. Agric. Food Chem. 59, 13147–13155 (2011).
pubmed: 22059381
doi: 10.1021/jf201702h
Wang, W. et al. Ulvan inhibits α-synuclein fibrillation and disrupts the mature fibrils: in vitro and in vivo studies. Int J. Biol. Macromol. 211, 580–591 (2022).
pubmed: 35561861
doi: 10.1016/j.ijbiomac.2022.05.045
Li, X., Chen, H. & Huang, K. β-synuclein regulates the phase transitions and amyloid conversion of α-synuclein. HK_natcomms_24-28818_data-AF2-data, https://doi.org/10.5281/zenodo.13637536 . (2024).