Review
Biochemistry & Molecular Biology
Surabhi Mehra, Laxmikant Gadhe, Riya Bera, Ajay Singh Sawner, Samir K. Maji
Summary: Abnormal accumulation of aggregated alpha-synuclein is a common feature in various neurodegenerative diseases, exhibiting clinical and pathological differences similar to prion disorders. Emerging evidence suggests that alpha-Syn self-assembles into conformationally diverse polymorphs, which may contribute to the clinical heterogeneity in synucleinopathies.
Review
Biochemistry & Molecular Biology
Jaime Santos, Irantzu Pallares, Salvador Ventura
Summary: This review focuses on the structural and mechanistic characterization of alpha-S synuclein oligomers, which are considered key pathogenic factors in synucleinopathies. Recent advances in understanding these elusive species have paved the way for targeting therapeutics and diagnosis.
Article
Multidisciplinary Sciences
Pratibha Kumari, Dhiman Ghosh, Agathe Vanas, Yanick Fleischmann, Thomas Wiegand, Gunnar Jeschke, Roland Riek, Cedric Eichmann
Summary: This study investigated the interaction between monomeric alpha-Syn and its fibrillar form using NMR and electron paramagnetic resonance spectroscopy, revealing that intermolecular interactions reduce intramolecular contacts in monomeric alpha-Syn, leading to further unfolding of its intrinsically disordered states and critically contributing to the aggregation kinetics of alpha-Syn during secondary nucleation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Reito Nakamura, Ikumi Tomizawa, Atsushi Iwai, Tetsuo Ikeda, Kota Hirayama, Yung Wen Chiu, Takanobu Suzuki, Airi Tarutani, Tatsuo Mano, Atsushi Iwata, Tatsushi Toda, Youhei Sohma, Motomu Kanai, Yukiko Hori, Taisuke Tomita
Summary: Aggregation of alpha-synuclein into amyloid is a pathological hallmark of neurodegenerative disorders, and inhibiting this aggregation can be a potential therapeutic strategy. This study demonstrates that photo-oxygenation using a photocatalyst successfully inhibits alpha-synuclein aggregation by reducing its seeding ability. The oxidation of histidine residue in alpha-synuclein is found to be responsible for this inhibitory effect.
Article
Biochemistry & Molecular Biology
Yu Zhang, Ying Wang, Yuying Liu, Guanghong Wei, Feng Ding, Yunxiang Sun
Summary: This study systematically investigated the structural ensembles and early aggregation dynamics of alpha-synuclein using atomistic discrete molecular dynamics simulations. The results showed that alpha-synuclein monomers and dimers mainly adopted unstructured formations, and dimerization enhanced beta-sheet formation, suggesting the critical role of beta-sheets in the amyloid aggregation of alpha-synuclein. The interaction between the C-terminus and the N-terminal tail and NAC region could prevent alpha-synuclein aggregation. These findings help to understand the nucleation and fibrillization of alpha-synuclein.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Joanna Zamel, Jiaxing Chen, Sofia Zaer, Paul David Harris, Paz Drori, Mario Lebendiker, Nir Kalisman, Nikolay V. Dokholyan, Eitan Lerner
Summary: Parkinson disease is associated with the aggregation of α-synuclein protein. In vitro experiments show that α-synuclein exists primarily as a monomer-dimer equilibrium in nanomolar to micromolar concentrations. By using cross-linking mass spectrometry and molecular dynamics simulations, a compact and stable dimer with partially exposed β-sheet structures is identified. This dimer, characterized by the proximity of tyrosine 39 hydroxyls, may play a role in the formation of α-synuclein amyloid fibrils and have etiological relevance to Parkinson disease.
Article
Chemistry, Multidisciplinary
Saurabh Awasthi, Cuifeng Ying, Jiali Li, Michael Mayer
Summary: This study demonstrates that resistive pulse measurements using polymer-coated solid-state nanopores enable single-particle-level characterization of the size and shape of individual amyloid oligomers in solution. Compared with conventional approaches, nanopore-based characterization provides superior resolution and rapid analysis in solution, which has the potential to become a widely accessible technique.
Article
Nanoscience & Nanotechnology
Dongtak Lee, Hyo Gi Jung, Dongsung Park, Junho Bang, Ji Hye Hong, Sang Won Lee, Seokbeom Roh, Jae Won Jang, Yonghwan Kim, Kyo Seon Hwang, Young-Sun Lee, Jae-Yong Park, In Duk Jung, Jeong Hoon Lee, Gyudo Lee, Dae Sung Yoon
Summary: We have developed a drug screening platform using amyloid-shelled gold nanocomplexes (ASGNs) to monitor the efficacy of alpha S-oligomer-degrading drugs. This platform mimics the in vivo generation process of pathological alpha S oligomers and has been tested using alpha S-degrading proteases and various small molecular substances with efficacy in PD treatment. Our results demonstrate that the ASGN-based in vitro platform has strong potential for discovering effective alpha S-oligomer-targeting drugs, thus reducing the attrition problem in drug discovery for PD treatment.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Neurosciences
Hiroaki Sekiya, Asato Tsuji, Yuki Hashimoto, Mariko Takata, Shunsuke Koga, Katsuya Nishida, Naonobu Futamura, Michi Kawamoto, Nobuo Kohara, Dennis W. Dickson, Hisatomo Kowa, Tatsushi Toda
Summary: The distribution of alpha SYN oligomers differs from Lewy-related pathology (LRP) in Parkinson's disease (PD), with alpha SYN oligomer burden being significantly greater in the neocortex and LRP being greater in vulnerable subcortical regions. In addition, alpha SYN oligomers in the hippocampus are associated with cognitive impairment in PD.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Henry M. Sanders, Blagojce Jovcevski, Michael T. Marty, Tara L. Pukala
Summary: The study demonstrates that lipid membrane composition influences the aggregation of misfolding proteins and the efficacy of amyloid inhibitors. Different mechanisms were observed for two well-known polyphenol inhibitors in the presence of lipid membranes, highlighting the importance of considering lipid environments in amyloid inhibitor design.
Article
Biochemistry & Molecular Biology
Kiryl Zhaliazka, Dmitry Kurouski
Summary: The aggregation of misfolded proteins is a key factor in Alzheimer's disease and Parkinson's disease, both of which are severe pathologies affecting millions of people worldwide. A study using nano-Infrared imaging technique investigated the structural organization of amyloid beta and alpha-synuclein fibrils in the brains of AD and PD patients. The researchers observed two different morphologically fibril polymorphs in each patient's brain, as well as the presence of lipids in the structure of alpha-synuclein fibrils, suggesting a potential role of lipid membranes in the onset and progression of PD.
Article
Biochemistry & Molecular Biology
Sapir Lan-Mark, Yifat Miller
Summary: This study investigates the specific interactions between monomers in polymorphic AS dimers at the molecular level using molecular modeling tools for the first time. The research reveals the role of both N-terminal and non-amyloidogenic component domains in the dimerization of all polymorphic AS dimers. Additionally, helices along the N-terminal of AS monomers hinder the contacts between monomers, thereby preventing nucleation or dimerization of AS.
ACS CHEMICAL NEUROSCIENCE
(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
Laxmikant Gadhe, Arunima Sakunthala, Semanti Mukherjee, Nitisha Gahlot, Riya Bera, Ajay Singh Sawner, Pradeep K. Kadu, Samir Maji
Summary: Although the pathogenic mechanism of synucleinopathies, including Parkinson's disease (PD), is not fully understood, α-synuclein (α-Syn) oligomers may play a significant role in the pathogenesis of PD. These oligomers are neurotoxic and may cause neuronal cell death. However, studying the structure and mechanisms of these oligomers is challenging due to their heterogeneity and transient nature. Understanding the formation and role of α-Syn oligomers can contribute to the development of new therapeutic approaches for PD.
BIOPHYSICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Irena Roterman, Katarzyna Stapor, Leszek Konieczny
Summary: The structural transformation producing amyloids provides new insights into the protein folding problem. Analysis of the polymorphic structures of a-synuclein amyloid reveals a dominant distribution consistent with the micelle-like system. This ordering of hydrophobicity distribution covers a spectrum from micelle-like forms to structures with different patterns, all influenced by the water environment and the common tendency of certain fragments of a-synuclein to accept micelle-like structuralization.
Article
Biochemistry & Molecular Biology
Adelin Gustot, Jose Ignacio Gallea, Rabia Sarroukh, Maria Soledad Celej, Jean-Marie Ruysschaert, Vincent Raussens
BIOCHEMICAL JOURNAL
(2015)
Article
Multidisciplinary Sciences
Niklas K. U. Koehler, Elke Stransky, Mirjam Meyer, Susanne Gaertner, Mona Shing, Martina Schnaldt, Maria S. Celej, Thomas M. Jovin, Thomas Leyhe, Christoph Laske, Anil Batra, Gerhard Buchkremer, Andreas J. Fallgatter, Dorothee Wernet, Elke Richartz-Salzburger
Article
Biochemistry & Molecular Biology
J. Ignacio Gallea, Rabia Sarroukh, Pablo Yunes-Quartino, Jean-Marie Ruysschaert, Vincent Raussens, M. Soledad Celej
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2016)
Article
Biochemistry & Molecular Biology
Maria Soledad Celej, Rabia Sarroukh, Erik Goormaghtigh, Gerardo D. Fidelio, Jean-Marie Ruysschaert, Vincent Raussens
BIOCHEMICAL JOURNAL
(2012)
Article
Pharmacology & Pharmacy
Martha Ines Burgos, Ricardo Ariel Fernandez, Maria Soledad Celej, Laura Isabel Rossi, Gerardo Daniel Fidelio, Sergio Alberto Dassie
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2011)
Article
Biophysics
M. Julia Roberti, Jonas Foelling, M. Soledad Celej, Mariano Bossi, Thomas M. Jovin, Elizabeth A. Jares-Erijman
BIOPHYSICAL JOURNAL
(2012)
Article
Biochemistry & Molecular Biology
Cesar L. Avila, Clarisa M. Torres-Bugeau, Leandro R. S. Barbosa, Elisa Morande Sales, Mohand O. Ouidja, Sergio B. Socias, M. Soledad Celej, Rita Raisman-Vozari, Dulce Papy-Garcia, Rosangela Itri, Rosana N. Chehin
JOURNAL OF BIOLOGICAL CHEMISTRY
(2014)
Article
Biochemistry & Molecular Biology
Jose Ignacio Gallea, Ernesto E. Ambroggio, Aldo Alejandro Vilcaes, Nicholas G. James, David M. Jameson, Maria Soledad Celej
JOURNAL OF NEUROCHEMISTRY
(2018)
Article
Oncology
Benjamin R. Smith, Marta B. Santos, Michael S. Marshall, Ludovico Cantuti-Castelvetri, Aurora Lopez-Rosas, Guannan Li, Richard van Breemen, Kumiko I. Claycomb, Jose I. Gallea, Maria S. Celej, Stephen J. Crocker, Maria I. Givogri, Ernesto R. Bongarzone
JOURNAL OF PATHOLOGY
(2014)
Article
Multidisciplinary Sciences
Niklas K. U. Koehler, Elke Stransky, Mona Shing, Susanne Gaertner, Mirjam Meyer, Brigitte Schreitmueller, Thomas Leyhe, Christoph Laske, Walter Maetzler, Phillipp Kahle, Maria S. Celej, Thomas M. Jovin, Andreas J. Fallgatter, Anil Batra, Gerhard Buchkremer, Klaus Schott, Elke Richartz-Salzburger
Article
Multidisciplinary Sciences
Claudio Bussi, Javier Maria Peralta Ramos, Daniela S. Arroyo, Emilia A. Gaviglio, Jose Ignacio Gallea, Ji Ming Wang, Maria Soledad Celej, Pablo Iribarren
SCIENTIFIC REPORTS
(2017)
Article
Multidisciplinary Sciences
Hazem Abdelkarim, Michael S. Marshall, Giuseppe Scesa, Rachael A. Smith, Emily Rue, Jeffrey Marshall, Vince Elackattu, Monika Stoskute, Yazan Issa, Marta Santos, Duc Nguyen, Zane Hauck, Richard van Breemen, Maria S. Celej, Vadim Gaponenko, Ernesto R. Bongarzone
SCIENTIFIC REPORTS
(2018)
Article
Cell Biology
Claudio Bussi, Javier M. Peralta Ramos, Daniela S. Arroyo, Jose Gallea, Paolo Ronchi, Androniki Kolovou, Ji M. Wang, Oliver Florey, Maria S. Celej, Yannick Schwab, Nicholas T. Ktistakis, Pablo Iribarren
JOURNAL OF CELL SCIENCE
(2018)
Review
Biochemistry & Molecular Biology
Carlos W. Bertoncini, M. Soledad Celej
CURRENT PROTEIN & PEPTIDE SCIENCE
(2011)