Liquid-liquid phase separation of α-Synuclein: A new mechanistic insight for α-Synuclein aggregation associated with Parkinson's disease pathogenesis.
Semanti Mukherjee,A. Sakunthala,Laxmikant G. Gadhe,Manisha Poudyal,Ajay Singh Sawner,Pradeep Kadu,Samir K. Maji +6 more
77
TL;DR: In this article , the authors demonstrate the recent development of α-Syn LLPS, the underlying mechanism along with the microscopic events of aberrant phase transition, and further discuss how several intrinsic and extrinsic factors regulate the thermodynamics and kinetics of αSynLLPS and co-LLPS with other proteins, which might explain the pathophysiology of α Syn in various neurodegenerative diseases.
read more
About: This article is published in Journal of Molecular Biology. The article was published on 01 Jul 2022. and is currently open access. The article focuses on the topics: Medicine & Synucleinopathies.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
The liquid-to-solid transition of FUS is promoted by the condensate surface.
Yi Shen,Anqi Chen,Wenyun Wang,Yinan Shen,Francesco Simone Ruggeri,Stefano Aime,Zizhao Wang,Seema Qamar,Jorge R. Espinosa,Adiran Garaizar,Peter St George-Hyslop,Rosana Collepardo-Guevara,David A. Weitz,Daniele Vigolo,Tuomas P. J. Knowles +14 more
TL;DR: It is revealed that condensates convert to a solid gel with inhomogeneous structures in both temporal and spatial dimensions, and it is demonstrated that this transition initiated at the condensates interface, providing the basis for strategies to influence this process when it occurs in disease.
64
Targeting Biomolecular Condensation and Protein Aggregation against Cancer.
Jerson L. Silva,Debora Foguel,Vitor F. Ferreira,Tuane C. R. G. Vieira,Mayra A. Marques,Giulia D. S. Ferretti,Tiago F. Outeiro,Yraima Cordeiro,Guilherme A. P. de Oliveira +8 more
TL;DR: In this paper , the dual nature of biomolecular condensates, spotlighting their role in cancer, particularly concerning the p53 tumor suppressor, was thoroughly examined, revealing that molecules capable of inhibiting mutant p53 aggregation can curtail tumor proliferation and migration.
32
Time-Dependent Material Properties of Aging Biomolecular Condensates from Different Viscoelasticity Measurements in Molecular Dynamics Simulations
TL;DR: In this article , the authors compared three different methods to measure the viscoelasticity of biomolecular condensates in molecular simulations, including shear stress relaxation modulus integration (SSRMI), the oscillatory shear (OS) technique, and the bead tracking (BT) method.
27
Distinct Effects of Familial Parkinson’s Disease-Associated Mutations on α-Synuclein Phase Separation and Amyloid Aggregation
TL;DR: In this article , the effects of five mutations associated with familial PD, A30P, E46K, H50Q, A53T, and A53E, on the phase separation of α-Syn were examined.
18
Protein misfolding and amyloid nucleation through liquid-liquid phase separation.
Semanti Mukherjee,Manisha Poudyal,Kritika Dave,Pradeep Kadu,Samir K. Maji +4 more
TL;DR: A generic LLPS-mediated multistep nucleation mechanism for amyloid aggregation and its implication in neurodegeneration is proposed and summarized.
18
References
Aggresomes: A Cellular Response to Misfolded Proteins
TL;DR: The intracellular fate of cystic fibrosis transmembrane conductance regulator (CFTR) is investigated and it is demonstrated that undegraded CFTR molecules accumulate at a distinct pericentriolar structure which is termed the aggresome.
Aggresomes, inclusion bodies and protein aggregation.
TL;DR: This work has suggested that, in animal cells, aggregated proteins are specifically delivered to inclusion bodies by dynein-dependent retrograde transport on microtubules and this microtubule-dependent inclusion body is called an aggresome.
2K
|[alpha]|-Synuclein is phosphorylated in synucleinopathy lesions
Hideo Fujiwara,Masato Hasegawa,Naoshi Dohmae,Akiko Kawashima,Eliezer Masliah,Matthew S. Goldberg,Jie Shen,Koji Takio,Takeshi Iwatsubo +8 more
TL;DR: It is shown by mass spectrometry analysis and studies with an antibody that specifically recognizes phospho-Ser 129 of α-synuclein, that this residue is selectively and extensively phosphorylated in synucleinopathy lesions and promoted fibril formation in vitro.
2K
α-synuclein locus duplication as a cause of familial Parkinson's disease
Marie-Christine Chartier-Harlin,Jennifer M. Kachergus,Christophe Roumier,Vincent Mouroux,Xavier Douay,Sarah Lincoln,Clotilde Levecque,Lydie Larvor,Joris Andrieux,Mary M. Hulihan,Nawal Waucquier,Luc Defebvre,Philippe Amouyel,Matthew J. Farrer,Alain Destée +14 more
TL;DR: The clinical phenotype of SNCA duplication closely resembles idiopathic Parkinson's disease, which has a late age-of-onset, progresses slowly, and in which neither cognitive decline nor dementia are prominent, and suggest a direct relation between S NCA gene dosage and disease progression.
2K
Protein Phase Separation: A New Phase in Cell Biology.
Steven Boeynaems,Steven Boeynaems,Simon Alberti,Nicolas L. Fawzi,Tanja Mittag,Magdalini Polymenidou,Frederic Rousseau,Frederic Rousseau,Joost Schymkowitz,Joost Schymkowitz,James Shorter,Benjamin Wolozin,Ludo Van Den Bosch,Peter Tompa,Peter Tompa,Monika Fuxreiter +15 more
TL;DR: A combination of techniques from cell biology, biophysics, physical chemistry, structural biology, and bioinformatics are starting to help establish the molecular principles of an emerging field, thus paving the way for exciting discoveries, including novel therapeutic approaches for the treatment of age-related disorders.
1.8K