AccScience Publishing / AN / Online First / DOI: 10.36922/an.4493
Submit to AN
Cite this article
7
Download
102
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
REVIEW ARTICLE

Liquid–liquid phase separation in neurodegenerative diseases: An updated understanding

Yiming Zhou1,2,3 ,  Xinlu Chen1,2,3 ,  Cihang Liu1 ,  Ying Wang4,5 ,  Tianjiao Xia2,3* ,  Xiaoping Gu1*
Show Less
1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department, Nanjing University, Nanjing, China
2 Medical School, Nanjing University, Nanjing, China
3 Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China
4 Department of Biochemistry and Biophysics, Beijing Key Laboratory of Protein Post-translational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
5 Center for Healthy Aging, Changzhi Medical College, Changzhi, China
Advanced Neurology, 4493 https://doi.org/10.36922/an.4493
Submitted: 11 August 2024 | Accepted: 13 November 2024 | Published: 16 December 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

Liquid–liquid phase separation (LLPS), once understood merely as a physicochemical phenomenon, has emerged over the past decade as a critical player in life processes. LLPS provides a novel framework for understanding the structure, function, and spatiotemporal regulation of intracellular biomolecules. Through LLPS, biomolecules within cells can spontaneously assemble into membraneless compartments, which allow precise regulation of biochemical reactions and influence critical cellular processes such as signal transduction and gene expression. Despite its recognized significance in basic biological research, the role of LLPS in human disease is still an area worthy of continued exploration. Currently, the most studied disorders in relation to LLPS are neurodegenerative diseases and cancer. In neurodegenerative diseases, LLPS is closely linked to protein misfolding and aggregation, processes that can lead to the formation of toxic assemblies, ultimately causing neuronal damage and death. In cancer, aberrant LLPS may contribute to the dysregulation of signaling pathways, promoting uncontrolled cell proliferation and metastasis. This review highlights recent advances regarding the role of LLPS in the pathogenesis of neurodegenerative diseases, discussing its function in these pathological conditions and proposing directions for future research. As research progresses, the potential role of LLPS in other human diseases will likely be uncovered, offering new avenues for diagnosis and therapy. Therefore, further investigation into the mechanisms of LLPS and its involvement in disease pathology will be crucial for advancing our understanding of human health and disease.

Keywords
Liquid–liquid phase separation
Neurodegenerative diseases
Protein aggregation
Signal transduction
Gene mutation
Funding
This work was supported by grants from the National Natural Science Foundation of China (Grant Numbers: 82171193, 81930035, 82230048, 92249303, and 91749208), the National Key R&D Program of China (Grant Number: 2018YFC2001901), Jiangsu Provincial Medical Key Discipline (Grant Number: ZDXK202232), and the Qing Lan Project.
Conflict of interest
Xiaoping Gu is an Editorial Board Member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
References
  1. Zhang H, Ji X, Li P, et al. Liquid-liquid phase separation in biology: Mechanisms, physiological functions and human diseases. Sci China Life Sci. 2020;63(7):953-985. doi: 10.1007/s11427-020-1702-x

 

  1. Elbaum-Garfinkle S, Kim Y, Szczepaniak K, et al. The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics. Proc Natl Acad Sci U S A. 2015;112(23):7189-7194. doi: 10.1073/pnas.1504822112

 

  1. Alberti S, Hyman AA. Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing. Nat Rev Mol Cell Biol. 2021;22(3):196-213. doi: 10.1038/s41580-020-00326-6

 

  1. Banani SF, Lee HO, Hyman AA, Rosen MK. Biomolecular condensates: Organizers of cellular biochemistry. Nat Rev Mol Cell Biol. 2017;18(5):285-298. doi: 10.1038/nrm.2017.7

 

  1. Gao C, Gu J, Zhang H, et al. Hyperosmotic-stress-induced liquid-liquid phase separation of ALS-related proteins in the nucleus. Cell Rep. 2022;40(3):111086. doi: 10.1016/j.celrep.2022.111086

 

  1. Wang B, Zhang L, Dai T, et al. Liquid-liquid phase separation in human health and diseases. Signal Transduct Target Ther. 2021;6(1):290. doi: 10.1038/s41392-021-00678-1

 

  1. Hayashi Y, Ford LK, Fioriti L, McGurk L, Zhang M. Liquid-liquid phase separation in physiology and pathophysiology of the nervous system. J Neurosci. 2021;41(5):834-844. doi: 10.1523/jneurosci.1656-20.2020

 

  1. Mathieu C, Pappu RV, Taylor JP. Beyond aggregation: Pathological phase transitions in neurodegenerative disease. Science. 2020;370(6512):56-60. doi: 10.1126/science.abb8032

 

  1. Zbinden A, Pérez-Berlanga M, De Rossi P, Polymenidou M. Phase separation and neurodegenerative diseases: A disturbance in the force. Dev Cell. 2020;55(1):45-68. doi: 10.1016/j.devcel.2020.09.014

 

  1. Hayes LR, Kalab P. Emerging therapies and novel targets for TDP-43 proteinopathy in ALS/FTD. Neurotherapeutics. 2022;19:1061-1084. doi: 10.1007/s13311-022-01260-5

 

  1. Garg DK, Bhat R. Modulation of assembly of TDP-43 low-complexity domain by heparin: From droplets to amyloid fibrils. Biophys J. 2022;121(13):2568-2582. doi: 10.1016/j.bpj.2022.05.042

 

  1. Sun Y, Zhang S, Hu J, et al. Molecular structure of an amyloid fibril formed by FUS low-complexity domain. iScience. 2022;25(1):103701. doi: 10.1016/j.isci.2021.103701

 

  1. Wu C, Zhao J, Wu Q, Tan Q, Liu Q, Xiao S. Tau N-terminal inserts regulate tau liquid-liquid phase separation and condensates maturation in a neuronal cell model. Int J Mol Sci. 2021;22(18):9728. doi: 10.3390/ijms22189728

 

  1. Hernández-Vega A, Braun M, Scharrel L, et al. Local nucleation of microtubule bundles through tubulin concentration into a condensed Tau phase. Cell Rep. 2017;20(10):2304-2312. doi: 10.1016/j.celrep.2017.08.042

 

  1. Gui X, Feng S, Li Z, et al. Liquid-liquid phase separation of amyloid-β oligomers modulates amyloid fibrils formation. J Biol Chem. 2023;299(3):102926. doi: 10.1016/j.jbc.2023.102926

 

  1. Yang J, Yang X. Phase transition of huntingtin: Factors and pathological relevance. Front Genet. 2020;11:754. doi: 10.3389/fgene.2020.00754

 

  1. Xu B, Huang S, Liu Y, et al. Manganese promotes α-synuclein amyloid aggregation through the induction of protein phase transition. J Biol Chem. 2022;298(1):101469. doi: 10.1016/j.jbc.2021.101469

 

  1. Ray S, Singh N, Kumar R, et al. α-Synuclein aggregation nucleates through liquid-liquid phase separation. Nat Chem. 2020;12(8):705-716. doi: 10.1038/s41557-020-0465-9

 

  1. Molliex A, Temirov J, Lee J, et al. Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization. Cell. 2015;163(1):123-133. doi: 10.1016/j.cell.2015.09.015

 

  1. Murakami T, Qamar S, Lin JQ, et al. ALS/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs RNP granule function. Neuron. 2015;88(4):678-690. doi: 10.1016/j.neuron.2015.10.030

 

  1. Faruk MO, Ichimura Y, Kageyama S, et al. Phase-separated protein droplets of amyotrophic lateral sclerosis-associated p62/SQSTM1 mutants show reduced inner fluidity. J Biol Chem. 2021;297(6):101405. doi: 10.1016/j.jbc.2021.101405

 

  1. Vendruscolo M, Fuxreiter M. Sequence determinants of the aggregation of proteins within condensates generated by liquid-liquid phase separation. J Mol Biol. 2022;434(1):167201. doi: 10.1016/j.jmb.2021.167201

 

  1. Keating SS, San Gil R, Swanson MEV, Scotter EL, Walker AK. TDP-43 pathology: From noxious assembly to therapeutic removal. Prog Neurobiol. 2022;211:102229. doi: 10.1016/j.pneurobio.2022.102229

 

  1. Wen J, Hong L, Krainer G, et al. Conformational expansion of tau in condensates promotes irreversible aggregation. J Am Chem Soc. 2021;143:13056-13064. doi: 10.1021/jacs.1c03078

 

  1. Wang C, Duan Y, Duan G, et al. Stress induces dynamic, cytotoxicity-antagonizing TDP-43 nuclear bodies via paraspeckle LncRNA NEAT1-mediated liquid-liquid phase separation. Mol Cell. 2020;79(3):443-458.e7. doi: 10.1016/j.molcel.2020.06.019

 

  1. Radulović S, Sunkara S, Maurer C, Leitinger G. Digging deeper: Advancements in visualization of inhibitory synapses in neurodegenerative disorders. Int J Mol Sci. 2021;22(22):12470. doi: 10.3390/ijms222212470

 

  1. Benarroch EE. Glutamatergic synaptic plasticity and dysfunction in Alzheimer disease: Emerging mechanisms. Neurology. 2018;91(3):125-132. doi: 10.1212/wnl.0000000000005807

 

  1. Citri A, Malenka RC. Synaptic plasticity: Multiple forms, functions, and mechanisms. Neuropsychopharmacology. 2008;33(1):18-41. doi: 10.1038/sj.npp.1301559

 

  1. Perrone-Capano C, Volpicelli F, Penna E, Chun JT, Crispino M. Presynaptic protein synthesis and brain plasticity: From physiology to neuropathology. Prog Neurobiol. 2021;202:102051. doi: 10.1016/j.pneurobio.2021.102051

 

  1. Liu PW, Hosokawa T, Hayashi Y. Regulation of synaptic nanodomain by liquid-liquid phase separation: A novel mechanism of synaptic plasticity. Curr Opin Neurobiol. 2021;69:84-92. doi: 10.1016/j.conb.2021.02.004

 

  1. Hosokawa T, Liu PW. Regulation of the stability and localization of post-synaptic membrane proteins by liquid-liquid phase separation. Front Physiol. 2021;12:795757.doi: 10.3389/fphys.2021.795757

 

  1. Milovanovic D, Rizzoli SO. Editorial: Protein phase separation and aggregation in (Patho) physiology of neurons. Front Physiol. 2022;13:959570. doi: 10.3389/fphys.2022.959570

 

  1. Liang M, Jin G, Xie X, et al. Oligomerized liprin-α promotes phase separation of ELKS for compartmentalization of presynaptic active zone proteins. Cell Rep. 2021;34(12):108901. doi: 10.1016/j.celrep.2021.108901

 

  1. Milovanovic D, Wu Y, Bian X, De Camilli P. A liquid phase of synapsin and lipid vesicles. Science. 2018;361(6402):604-607. doi: 10.1126/science.aat5671

 

  1. Wu X, Cai Q, Shen Z, et al. RIM and RIM-BP form presynaptic active-zone-like condensates via phase separation. Mol Cell. 2019;73(5):971-984.e5. doi: 10.1016/j.molcel.2018.12.007

 

  1. Chen X, Wu X, Wu H, Zhang M. Phase separation at the synapse. Nat Neurosci. 2020;23(3):301-310. doi: 10.1038/s41593-019-0579-9

 

  1. Zeng M, Chen X, Guan D, et al. Reconstituted postsynaptic density as a molecular platform for understanding synapse formation and plasticity. Cell. 2018;174(5):1172-1187.e16. doi: 10.1016/j.cell.2018.06.047

 

  1. Zeng M, Shang Y, Araki Y, Guo T, Huganir RL, Zhang M. Phase transition in postsynaptic densities underlies formation of synaptic complexes and synaptic plasticity. Cell. 2016;166(5):1163-1175.e12. doi: 10.1016/j.cell.2016.07.008

 

  1. Christensen NR, Pedersen CP, Sereikaite V, et al. Bidirectional protein-protein interactions control liquid-liquid phase separation of PSD-95 and its interaction partners. iScience. 2022;25(2):103808. doi: 10.1016/j.isci.2022.103808

 

  1. Letts VA, Felix R, Biddlecome GH, et al. The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit. Nat Genet. 1998;19(4):340-347. doi: 10.1038/1228

 

  1. Zeng M, Díaz-Alonso J, Ye F, et al. Phase separation-mediated TARP/MAGUK complex condensation and AMPA receptor synaptic transmission. Neuron. 2019;104(3):529-543.e6. doi: 10.1016/j.neuron.2019.08.001

 

  1. Araki Y, Zeng M, Zhang M, Huganir RL. Rapid dispersion of SynGAP from synaptic spines triggers AMPA receptor insertion and spine enlargement during LTP. Neuron. 2015;85(1):173-189. doi: 10.1016/j.neuron.2014.12.023

 

  1. Araki Y, Hong I, Gamache TR, et al. SynGAP isoforms differentially regulate synaptic plasticity and dendritic development. Elife. 2020;9:e56273. doi: 10.7554/eLife.56273

 

  1. Patel A, Lee HO, Jawerth L, et al. A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell. 2015;162(5):1066-1077. doi: 10.1016/j.cell.2015.07.047

 

  1. Mackenzie IR, Nicholson AM, Sarkar M, et al. TIA1 mutations in amyotrophic lateral sclerosis and frontotemporal dementia promote phase separation and alter stress granule dynamics. Neuron. 2017;95(4):808-816.e9. doi: 10.1016/j.neuron.2017.07.025

 

  1. Conicella AE, Zerze GH, Mittal J, Fawzi NL. ALS mutations disrupt phase separation mediated by α-helical structure in the TDP-43 low-complexity C-terminal domain. Structure. 2016;24(9):1537-1549. doi: 10.1016/j.str.2016.07.007

 

  1. Murray DT, Kato M, Lin Y, et al. Structure of FUS protein fibrils and its relevance to self-assembly and phase separation of low-complexity domains. Cell. 2017;171(3):615-627.e16. doi: 10.1016/j.cell.2017.08.048

 

  1. Solomon DA, Smikle R, Reid MJ, Mizielinska S. Altered phase separation and cellular impact in C9orf72-Linked ALS/FTD. Front Cell Neurosci. 2021;15:664151. doi: 10.3389/fncel.2021.664151

 

  1. Wang J, Choi JM, Holehouse AS, et al. A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins. Cell. 2018;174(3):688-699.e16. doi: 10.1016/j.cell.2018.06.006

 

  1. Zhou J, Chuang Y, Redding-Ochoa J, et al. The autophagy adaptor TRIAD3A promotes tau fibrillation by nested phase separation. Nat Cell Biol. 2024;26(8):1274-1286. doi: 10.1038/s41556-024-01461-4

 

  1. Beijer D, Kim HJ, Guo L, et al. Characterization of HNRNPA1 mutations defines diversity in pathogenic mechanisms and clinical presentation. JCI Insight. 2021;6(14):e148363. doi: 10.1172/jci.insight.148363

 

  1. Ryan VH, Perdikari TM, Naik MT, et al. Tyrosine phosphorylation regulates hnRNPA2 granule protein partitioning and reduces neurodegeneration. EMBO J. 2021;40(3):e105001. doi: 10.15252/embj.2020105001

 

  1. Yu H, Lu S, Gasior K, et al. HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells. Science. 2021;371(6529):eabb4309. doi: 10.1126/science.abb4309

 

  1. Scherer NM, Maurel C, Graus MS, et al. RNA-binding properties orchestrate TDP-43 homeostasis through condensate formation in vivo. Nucleic Acids Res. 2024;52(9):5301-5319. doi: 10.1093/nar/gkae112

 

  1. Mee Hayes E, Sirvio L, Ye Y. A potential mechanism for targeting aggregates with proteasomes and disaggregases in liquid droplets. Front Aging Neurosci. 2022;14:854380. doi: 10.3389/fnagi.2022.854380

 

  1. Riley JF, Fioramonti PJ, Rusnock AK, Hehnly H, Castañeda CA. ALS-linked mutations impair UBQLN2 stress-induced biomolecular condensate assembly in cells. J Neurochem. 2021;159:145-155. doi: 10.1111/jnc.15453

 

  1. Sharkey LM, Safren N, Pithadia AS, et al. Mutant UBQLN2 promotes toxicity by modulating intrinsic self-assembly. Proc Natl Acad Sci U S A. 2018;115(44):E10495-E10504. doi: 10.1073/pnas.1810522115

 

  1. Deng Q, Holler CJ, Taylor G, et al. FUS is phosphorylated by DNA-PK and accumulates in the cytoplasm after DNA damage. J Neurosci. 2014;34(23):7802-7813. doi: 10.1523/jneurosci.0172-14.2014

 

  1. Jeppesen DK, Bohr VA, Stevnsner T. DNA repair deficiency in neurodegeneration. Prog Neurobiol. 2011;94(2):166-200. doi: 10.1016/j.pneurobio.2011.04.013

 

  1. Naumann M, Pal A, Goswami A, et al. Impaired DNA damage response signaling by FUS-NLS mutations leads to neurodegeneration and FUS aggregate formation. Nat Commun. 2018;9(1):335. doi: 10.1038/s41467-017-02299-1

 

  1. Singatulina AS, Hamon L, Sukhanova MV, et al. PARP-1 activation directs FUS to DNA damage sites to form PARG-reversible compartments enriched in damaged DNA. Cell Rep. 2019;27(6):1809-1821.e5. doi: 10.1016/j.celrep.2019.04.031

 

  1. Oshidari R, Huang R, Medghalchi M, et al. DNA repair by Rad52 liquid droplets. Nat Commun. 2020;11(1):695. doi: 10.1038/s41467-020-14546-z

 

  1. Krause LJ, Herrera MG, Winklhofer KF. The role of ubiquitin in regulating stress granule dynamics. Front Physiol. 2022;13:910759. doi: 10.3389/fphys.2022.910759

 

  1. Agarwal A, Arora L, Rai SK, Avni A, Mukhopadhyay S. Spatiotemporal modulations in heterotypic condensates of prion and α-synuclein control phase transitions and amyloid conversion. Nat Commun. 2022;13(1):1154. doi: 10.1038/s41467-022-28797-5

 

  1. Jin X, Zhou M, Chen S, Li D, Cao X, Liu B. Effects of pH alterations on stress- and aging-induced protein phase separation. Cell Mol Life Sci. 2022;79(7):380. doi: 10.1007/s00018-022-04393-0

 

  1. Cha SJ, Lee S, Choi HJ, et al. Therapeutic modulation of GSTO activity rescues FUS-associated neurotoxicity via deglutathionylation in ALS disease models. Dev Cell. 2022;57(6):783-798.e8. doi: 10.1016/j.devcel.2022.02.022

 

  1. Savastano A, Flores D, Kadavath H, Biernat J, Mandelkow E, Zweckstetter M. Disease-associated tau phosphorylation hinders tubulin assembly within tau condensates. Angew Chem Int Ed Engl. 2021;60(2):726-730. doi: 10.1002/anie.202011157

 

  1. Owen I, Shewmaker F. The role of post-translational modifications in the phase transitions of intrinsically disordered proteins. Int J Mol Sci. 2019;20(21):5501. doi: 10.3390/ijms20215501

 

  1. Huang S, Xu B, Liu Y. Calcium promotes α-synuclein liquid-liquid phase separation to accelerate amyloid aggregation. Biochem Biophys Res Commun. 2022;603:13-20. doi: 10.1016/j.bbrc.2022.02.097

 

  1. Grese ZR, Bastos AC, Mamede LD, French RL, Miller TM, Ayala YM. Specific RNA interactions promote TDP-43 multivalent phase separation and maintain liquid properties. EMBO Rep. 2021;22(12):e53632. doi: 10.15252/embr.202153632

 

  1. Gao YY, Zhong T, Wang LQ, et al. Zinc enhances liquid-liquid phase separation of Tau protein and aggravates mitochondrial damages in cells. Int J Biol Macromol. 2022;209(Pt A):703-715. doi: 10.1016/j.ijbiomac.2022.04.034

 

  1. Patel A, Malinovska L, Saha S, et al. ATP as a biological hydrotrope. Science. 2017;356(6339):753-756. doi: 10.1126/science.aaf6846

 

  1. Mann JR, Donnelly CJ. RNA modulates physiological and neuropathological protein phase transitions. Neuron. 2021;109:2663-2681. doi: 10.1016/j.neuron.2021.06.023

 

  1. Sanchez-Burgos I, Espinosa JR, Joseph JA, Collepardo- Guevara R. RNA length has a non-trivial effect in the stability of biomolecular condensates formed by RNA-binding proteins. PLoS Comput Biol. 2022;18(2):e1009810. doi: 10.1371/journal.pcbi.1009810

 

  1. Agarwal A, Rai SK, Avni A, Mukhopadhyay S. An intrinsically disordered pathological prion variant Y145Stop converts into self-seeding amyloids via liquid-liquid phase separation. Proc Natl Acad Sci U S A. 2021;118(45):e2100968118. doi: 10.1073/pnas.2100968118

 

  1. Hochmair J, Exner C, Franck M, et al. Molecular crowding and RNA synergize to promote phase separation, microtubule interaction, and seeding of Tau condensates. EMBO J. 2022;41(11):e108882. doi: 10.15252/embj.2021108882

 

  1. Venkatramani A, Mukherjee S, Kumari A, Panda D. Shikonin impedes phase separation and aggregation of tau and protects SH-SY5Y cells from the toxic effects of tau oligomers. Int J Biol Macromol. 2022;204:19-33. doi: 10.1016/j.ijbiomac.2022.01.172

 

  1. Zhang X, Lin Y, Eschmann NA, et al. RNA stores tau reversibly in complex coacervates. PLoS Biol. 2017;15(7):e2002183. doi: 10.1371/journal.pbio.2002183

 

  1. Rhine K, Dasovich M, Yoniles J, et al. Poly(ADP-ribose) drives condensation of FUS via a transient interaction. Mol Cell. 2022;82(5):969-985.e11. doi: 10.1016/j.molcel.2022.01.018

 

  1. Han Y, Ye H, Li P, et al. In vitro characterization and molecular dynamics simulation reveal mechanism of 14-3- 3ζ regulated phase separation of the tau protein. Int J Biol Macromol. 2022;208:1072-1081. doi: 10.1016/j.ijbiomac.2022.03.215

 

  1. Rekhi S, Garcia CG, Barai M, et al. Expanding the molecular language of protein liquid-liquid phase separation. Nat Chem. 2024;16(7):1113-1124. doi: 10.1038/s41557-024-01489-x

 

  1. Ye S, Latham AP, Tang Y, et al. Micropolarity governs the structural organization of biomolecular condensates. Nat Chem Biol. 2024;20(4):443-451. doi: 10.1038/s41589-023-01477-1

 

  1. Choi S, Meyer MO, Bevilacqua PC, Keating CD. Phase-specific RNA accumulation and duplex thermodynamics in multiphase coacervate models for membraneless organelles. Nat Chem. 2022;14(10):1110-1117. doi: 10.1038/s41557-022-00980-7

 

  1. Wang H, Kelley FM, Milovanovic D, Schuster BS, Shi Z. Surface tension and viscosity of protein condensates quantified by micropipette aspiration. Biophys Rep (N Y). 2021;1(1):100011. doi: 10.1016/j.bpr.2021.100011

 

  1. Lafontaine DLJ, Riback JA, Bascetin R, Brangwynne CP. The nucleolus as a multiphase liquid condensate. Nat Rev Mol Cell Biol. 2021;22(3):165-182. doi: 10.1038/s41580-020-0272-6

 

  1. Kilgore HR, Mikhael PG, Overholt KJ, et al. Distinct chemical environments in biomolecular condensates. Nat Chem Biol. 2024;20(3):291-301. doi: 10.1038/s41589-023-01432-0

 

  1. Alberti S, Gladfelter A, Mittag T. Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates. Cell. 2019;176(3):419-434. doi: 10.1016/j.cell.2018.12.035

 

  1. Fischer AAM, Robertson HB, Kong D, et al. Engineering material properties of transcription factor condensates to control gene expression in mammalian cells and mice. Small. 2024:e2311834. doi: 10.1002/smll.202311834

 

  1. Lee M, Moon HC, Jeong H, Kim DW, Park HY, Shin Y. Optogenetic control of mRNA condensation reveals an intimate link between condensate material properties and functions. Nat Commun. 2024;15(1):3216. doi: 10.1038/s41467-024-47442-x

 

  1. Capasso Palmiero U, Paganini C, Kopp MRG, Linsenmeier M, Küffner AM, Arosio P. Programmable zwitterionic droplets as biomolecular sorters and model of membraneless organelles. Adv Mater. 2022;34(4):e2104837. doi: 10.1002/adma.202104837

 

  1. Mitrea DM, Mittasch M, Gomes BF, Klein IA, Murcko MA. Modulating biomolecular condensates: A novel approach to drug discovery. Nat Rev Drug Discov. 2022;21(11):841-862. doi: 10.1038/s41573-022-00505-4

 

  1. Chakraborty S, Nandi P, Mishra J, et al. Molecular mechanisms in regulation of autophagy and apoptosis in view of epigenetic regulation of genes and involvement of liquid-liquid phase separation. Cancer Lett. 2024;587:216779. doi: 10.1016/j.canlet.2024.216779

 

  1. Li J, Gao J, Wang R. Control of chromatin organization and chromosome behavior during the cell cycle through phase separation. Int J Mol Sci. 2021;22(22):12271. doi: 10.3390/ijms222212271

 

  1. Nesterov SV, Ilyinsky NS, Plokhikh KS, et al. Order wrapped in chaos: On the roles of intrinsically disordered proteins and RNAs in the arrangement of the mitochondrial enzymatic machines. Int J Biol Macromol. 2024;267(Pt 1):131455. doi: 10.1016/j.ijbiomac.2024.131455

 

  1. Sansevrino R, Hoffmann C, Milovanovic D. Condensate biology of synaptic vesicle clusters. Trends Neurosci. 2023;46(4):293-306. doi: 10.1016/j.tins.2023.01.001

 

  1. Zhang L, Wang S, Wang W, et al. Phase-separated subcellular compartmentation and related human diseases. Int J Mol Sci. 2022;23(10):5491. doi: 10.3390/ijms23105491

 

  1. Zhang Y, Wei H, Wen W. Phase separation and mechanical forces in regulating asymmetric cell division of neural stem cells. Int J Mol Sci. 2021;22(19):10267.doi: 10.3390/ijms221910267

 

  1. McSwiggen DT, Mir M, Darzacq X, Tjian R. Evaluating phase separation in live cells: Diagnosis, caveats, and functional consequences. Genes Dev. 2019;33(23-24):1619-1634. doi: 10.1101/gad.331520.119

 

  1. Yoshida SR, Maity BK, Chong S. Visualizing protein localizations in fixed cells: Caveats and the underlying mechanisms. J Phys Chem B. 2023;127(19):4165-4173. doi: 10.1021/acs.jpcb.3c01658

 

  1. Irgen-Gioro S, Yoshida S, Walling V, Chong S. Fixation can change the appearance of phase separation in living cells. Elife. 2022;11:e79903. doi: 10.7554/eLife.79903

 

  1. Poudyal M, Patel K, Gadhe L, et al. Intermolecular interactions underlie protein/peptide phase separation irrespective of sequence and structure at crowded milieu. Nat Commun. 2023;14(1):6199. doi: 10.1038/s41467-023-41864-9

 

  1. Farahi N, Lazar T, Wodak SJ, Tompa P, Pancsa R. Integration of data from liquid-liquid phase separation databases highlights concentration and dosage sensitivity of LLPS drivers. Int J Mol Sci. 2021;22(6):3017. doi: 10.3390/ijms22063017

 

  1. Watson JL, Seinkmane E, Styles CT, et al. Macromolecular condensation buffers intracellular water potential. Nature. 2023;623(7988):842-852. doi: 10.1038/s41586-023-06626-z
Next article in this issue
Share
Back to top
Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept