Article
Multidisciplinary Sciences
Sabine M. Ulamec, Roberto Maya-Martinez, Emily J. Byrd, Katherine M. Dewison, Yong Xu, Leon F. Willis, Frank Sobott, George R. Heath, Patricija van Oosten Hawle, Vladimir L. Buchman, Sheena E. Radford, David J. Brockwell
Summary: In this study, the authors characterized the impact of amino acid substitution on alpha-synuclein aggregation. They found that residues 38 and 42 within the P1 region of alpha-synuclein influence amyloid formation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Masatomo So, Yuto Kimura, Keiichi Yamaguchi, Toshihiko Sugiki, Toshimichi Fujiwara, Cesar Aguirre, Kensuke Ikenaka, Hideki Mochizuki, Yasushi Kawata, Yuji Goto
Summary: The study found that polyphenols such as EGCG and KG have different effects on amyloid formation of proteins related to neurodegenerative diseases, which are associated with the solubility of polyphenols.
Article
Multidisciplinary Sciences
Jaime Santos, Pablo Gracia, Susanna Navarro, Samuel Pena-Diaz, Jordi Pujols, Nunilo Cremades, Irantzu Pallares, Salvador Ventura
Summary: Researchers have identified a class of peptides that can bind toxic α-synuclein oligomers and amyloid fibrils without interfering with monomeric functional protein, preventing further aggregation and associated cell damage.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Fengjuan Huang, Ying Wang, Yu Zhang, Chuang Wang, Jiangfang Lian, Feng Ding, Yunxiang Sun
Summary: The pathological aggregation of α-synuclein into amyloid fibrils is characteristic of Parkinson's disease. Repeats R3 and R6 play a crucial role in α-synuclein's aggregation, as they readily self-assemble into β-sheet-rich oligomers. R6 acts as the primary amyloidogenic core buried inside the central β-core, attracting neighboring repeats to form β-sheets, while R3 serves as a secondary amyloidogenic core, forming independent β-sheets in the fibril. These findings highlight the significance of R3 and R6 repeats in α-synuclein's amyloid aggregation and suggest their potential as targets for amyloid inhibitors.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Yifei Yao, Yiming Tang, Yun Zhou, Zhongyuan Yang, Guanghong Wei
Summary: This study reveals that the disruptive effects and modes of baicalein on alpha-synuclein fibrils are polymorphism-dependent. It can damage both WT and E46K/H50Q mutant alpha-synuclein fibrils, making it a potential drug candidate to alleviate the pathological process of Parkinson's disease.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Neurosciences
Juan Estaun-Panzano, Marie-Laure Arotcarena, Erwan Bezard
Summary: Synucleinopathies are a group of diseases characterized by the misfolding and aggregation of alpha-synuclein, leading to the formation of Lewy bodies. Studying the aggregation of alpha-synuclein is crucial for understanding these diseases, and recent breakthroughs have provided new insights into their mechanisms.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Fiamma A. Buratti, Nicola Boeffinger, Hugo A. Garro, Jesica S. Flores, Francisco J. Hita, Phelippe do Carmo Goncalves, Federico dos Reis Copello, Leonardo Lizarraga, Giulia Rossetti, Paolo Carloni, Markus Zweckstetter, Tiago F. Outeiro, Stefan Eimer, Christian Griesinger, Claudio O. Fernandez
Summary: In this study, we investigated the structural details of alpha S and its role in amyloid fibril assembly and lipid-binding. Our findings demonstrate that the aromaticity at position 39 of alpha S strongly influences its aggregation properties and membrane-bound conformations. This research provides new insights into the physiological and pathological events related to alpha S.
Article
Biochemistry & Molecular Biology
Marija Dubackic, Ilaria Idini, Veronica Lattanzi, Yun Liu, Anne Martel, Ann Terry, Michael Haertlein, Juliette M. Devos, Andrew Jackson, Emma Sparr, Sara Linse, Ulf Olsson
Summary: The accumulation of alpha-Synuclein fibrils in neurons is strongly associated with Parkinson's disease, with these fibrils forming dense clusters and exhibiting a mass fractal structure with a fractal dimension of d = 2.6 +/- 0.3. A simple model of rigid-rod clusters can reproduce this fractal dimension, indicating an effect of attractive fibril-fibril interactions on the clustering in Lewy body formation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Multidisciplinary Sciences
Ryan P. McGlinchey, Xiaodan Ni, Jared A. Shadish, Jiansen Jiang, Jennifer C. Lee
Summary: The study demonstrates that C-terminal truncations can accelerate the aggregation of alpha-synuclein, while the role of N-terminal truncations remains unclear. The research found that N-terminal truncations modulated the aggregation kinetics and fibril morphologies of alpha-synuclein.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Simona S. Ghanem, Hend S. Fayed, Qi Zhu, Jia-Hong Lu, Nishant N. Vaikath, Janarthanan Ponraj, Said Mansour, Omar M. A. El-Agnaf
Summary: The accumulation and aggregation of alpha-synuclein is a key pathological event in Parkinson's disease and related disorders. Screening natural alkaloid compounds from Chinese medicinal herbs, researchers identified six compounds that inhibit alpha-synuclein-seeded fibril formation and toxicity, suggesting a promising therapeutic strategy for synucleinopathies.
Article
Chemistry, Multidisciplinary
Tinna Palmadottir, Anders Malmendal, Thom Leiding, Mikael Lund, Sara Linse
Summary: The study reveals a significant increase in pH during fibril formation of a-synuclein, indicating proton uptake during the process. Fibril formation leads to a significant increase in the average pK(a) value of acidic residues and also results in a significant change in proton binding capacitance.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Simona S. Ghanem, Nour K. Majbour, Nishant N. Vaikath, Mustafa T. Ardah, Daniel Erskine, Nanna Moller Jensen, Muneera Fayyad, Indulekha P. Sudhakaran, Eftychia Vasili, Katerina Melachroinou, Ilham Y. Abdi, Ilaria Poggiolini, Patricia Santos, Anton Dorn, Paolo Carloni, Kostas Vekrellis, Johannes Attems, Ian McKeith, Tiago F. Outeiro, Poul Henning Jensen, Omar M. A. El-Agnaf
Summary: The phosphorylation of alpha-synuclein at serine 129 inhibits fibril formation and appears to have a protective role in the aggregation process, which has implications for understanding the pathobiology of Lewy body disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Neurosciences
Aditya Iyer, Arshdeep Sidhu, Vinod Subramaniam
Summary: N-alpha-acetylation is a common post-translational modification in eukaryotic proteins, which has significant effects on protein regulation and function. However, the precise mechanisms and implications of N-alpha-acetylation of alpha-synuclein (alpha S) are not fully understood. This review provides an overview of current knowledge and discusses the impact of N-alpha-acetylation on the conformational, oligomeric, and fibrillar states of alpha S, as well as its relevance to Lewy body formation and synucleinopathies.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Leif Antonschmidt, Riza Dervisoglu, Vrinda Sant, Kumar Tekwani Movellan, Ingo Mey, Dietmar Riedel, Claudia Steinem, Stefan Becker, Loren B. Andreas, Christian Griesinger
Summary: Recent advances in the structural biology of disease-relevant alpha-synuclein fibrils have shed light on a variety of structures, while investigations into the aggregation process have identified key time points for the isolation of prefibrillar and early fibrillar intermediates, revealing a segmental folding process.
Article
Biochemistry & Molecular Biology
Sneha Jos, Hemanga Gogoi, Thazhe Kootteri Prasad, Manjunath A. Hurakadli, Neelagandan Kamariah, Balasundaram Padmanabhan, Sivaraman Padavattan
Summary: The study reveals the role of alpha-Synuclein in Parkinson's disease through specific binding to histones, with the phosphorylation mimicking mutant showing higher affinity for proteins involved in Lewy body formation. The interaction with dsDNA was found to be weak and nonspecific. This suggests that alpha-Synuclein's nuclear function may be driven through histone interaction.
Meeting Abstract
Biophysics
Kseniia Afitska, Volodymyr V. Shvadchak, Dmytro A. Yushchenko
BIOPHYSICAL JOURNAL
(2019)
Article
Biochemistry & Molecular Biology
Kseniia Afitska, Anastasiia Priss, Dmytro A. Yushchenko, Volodymyr V. Shvadchak
JOURNAL OF MOLECULAR BIOLOGY
(2020)
Article
Chemistry, Physical
Jord C. Prangsma, Robert Molenaar, Laura van Weeren, Daphne S. Bindels, Lindsay Haarbosch, Jente Stouthamer, Theodorus W. J. Gadella, Vinod Subramaniam, Willem L. Vos, Christian Blum
JOURNAL OF PHYSICAL CHEMISTRY B
(2020)
Article
Chemistry, Multidisciplinary
Dmytro Sysoiev, Eliska Prochazkova, Aleksander Semenenko, Radek Pohl, Svitlana Shishkina, Blanka Klepetarova, Volodymyr Shvadchak, Dmytro A. Yushchenko
Article
Biochemistry & Molecular Biology
Andrii S. Kurochka, Dmytro A. Yushchenko, Petr Bour, Volodymyr V. Shvadchak
Summary: The presence of lipids significantly delays the fibrillization process of the alpha-Synuclein protein, with membrane-bound protein not being involved in fibril elongation.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Physical
Theresa S. Braun, Juliane Stehle, Sylwia Kacprzak, Patrick Carl, Peter Hoefer, Vinod Subramaniam, Malte Drescher
Summary: Protein-membrane interactions are crucial for cellular processes, and the study of these interactions presents a challenge in modern biophysical chemistry. By employing rapid-scan electron paramagnetic resonance spectroscopy, the interaction between αS and negatively charged vesicles in vitro was studied, with reflections observed in cells as well.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Pankaj Gaur, Maksym Galkin, Andrii Kurochka, Subrata Ghosh, Dmytro A. Yushchenko, Volodymyr V. Shvadchak
Summary: In this study, two molecular rotor-based probes RB1 and RB2 are presented, with RB1 showing outstanding absorption red-shift and high fluorescence enhancement, exhibiting high affinity and selective staining ability for alpha-synuclein fibrils in living cells. RB1 can be used for intracellular imaging of alpha-synuclein fibrils due to its strong binding affinity and cell-permeable nature.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Medicinal
Anastasiia Priss, Kseniia Afitska, Maksym Galkin, Dmytro A. Yushchenko, Volodymyr V. Shvadchak
Summary: By engineering protein inhibitors with higher affinity for fibrils, this study demonstrates the potential to inhibit the misfolding of alpha Syn into amyloid fibrils, presenting a promising therapeutic approach for Parkinson's disease. These inhibitors are selective to misfolded alpha Syn, non-toxic, and active in small concentrations, showing potential to slow down the progression of PD by suppressing the formation of pathological aggregates in cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Maksym Galkin, Anastasiia Priss, Oleksandra Topcheva, Dmytro A. Yushchenko, Volodymyr V. Shvadchak
Summary: A novel cell-based assay using FRET technology was developed to test inhibitors of alpha Syn aggregation, providing a reliable alternative to traditional cell viability assays. This assay has the potential to facilitate drug development for Parkinson's disease by identifying non-specific inhibitors and allowing for high-throughput screening.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Anna Poryvai, Maksym Galkin, Volodymyr Shvadchak, Tomas Slanina
Summary: In this work, a water-soluble caging group based on a pi-extended BODIPY scaffold was developed to release carboxylate-containing cargo upon red light illumination. Mechanistic studies showed new insights into the photoreactivity of these cages, and the structure of the carboxylate cargo was found to significantly influence the rate and efficiency of the uncaging process. The method was successfully used for selective delivery, visualization, and photorelease of a signaling lipid in cell plasma and internal membranes, inducing Ca2+ release in cells expressing the GPR40 receptor.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Neurosciences
Aditya Iyer, Arshdeep Sidhu, Vinod Subramaniam
Summary: N-alpha-acetylation is a common post-translational modification in eukaryotic proteins, which has significant effects on protein regulation and function. However, the precise mechanisms and implications of N-alpha-acetylation of alpha-synuclein (alpha S) are not fully understood. This review provides an overview of current knowledge and discusses the impact of N-alpha-acetylation on the conformational, oligomeric, and fibrillar states of alpha S, as well as its relevance to Lewy body formation and synucleinopathies.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Maksym Galkin, Oleksandra Topcheva, Anastasiia Priss, Tatiana Borisova, Volodymyr V. Shvadchak
Summary: Parkinson's disease is characterized by the death of certain neurons in the midbrain and the accumulation of alpha-synuclein fibrils. Current treatment involves increasing dopamine levels, but this can produce toxic oligomers. In our study, we found that these oligomers can inhibit alpha-synuclein fibrillization, providing insights into the effects of dopamine-enhancing therapy on Parkinson's disease.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Pankaj Gaur, Maksym Galkin, Sebastian Hauke, Ruslan Redkin, Carolyn Barnes, Volodymyr V. Shvadchak, Dmytro A. Yushchenko
CHEMICAL COMMUNICATIONS
(2020)
Meeting Abstract
Biophysics
Yevhenii Kyriukha, Kseniia Afitska, Andrii Kurochka, Shubhra Sachan, Dmytro Yushchenko, Volodymyr Shvadchak
BIOPHYSICAL JOURNAL
(2020)
Article
Chemistry, Multidisciplinary
Pankaj Gaur, Oleksandr A. Kucherak, Yulia G. Ermakova, Volodymyr V. Shvadchak, Dmytro A. Yushchenko
CHEMICAL COMMUNICATIONS
(2019)
