Review
Biochemistry & Molecular Biology
Parveen Salahuddin, Munazza Tamkeen Fatima, Vladimir N. Uversky, Rizwan Hasan Khan, Zeyaul Islam, Mohammad Furkan
Summary: Neurodegenerative diseases are characterized by the abnormal loss of neurons, with common pathogenic mechanisms involving misfolding and aggregation of proteins. Accumulating evidence suggests that amyloid oligomers, not fibrils, are the most toxic species causing AD and PD.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Pharmacology & Pharmacy
Samuel Pena-Diaz, Javier Garcia-Pardo, Salvador Ventura
Summary: Parkinson's disease is the second most common neurodegenerative disorder worldwide, characterized by protein deposits in dopaminergic neurons. Recent research has identified compounds primarily of an aromatic nature that target a-Syn aggregation. This study provides a historical overview of Parkinson's disease, its molecular aspects, and current trends in small compound development to address a-Syn aggregation. These compounds are promising for the development of effective therapies for Parkinson's disease.
Article
Neurosciences
Daniel Kam Yin Chan, Nady Braidy, Ren Fen Chen, Ying Hua Xu, Steven Bentley, Michal Lubomski, Ryan L. Davis, Jack Chen, Carolyn M. Sue, George D. Mellick
Summary: This study investigated the correlation between plasma levels of alpha-synuclein, anti-alpha-synuclein, and their ratios to amyloid beta-40 in Parkinson's disease diagnosis. A diagnostic algorithm was built using promising biomarkers, and the results were verified in an independent sample. The study showed that the combination of these biomarkers demonstrated promising sensitivity and specificity.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Chemistry, Analytical
Yu P. Zhang, Evgeniia Lobanova, Derya Emin, Sergey V. Lobanov, Antonina Kouli, Caroline H. Williams-Gray, David Klenerman
Summary: This study introduces a new method for the diagnosis of early Parkinson's disease. The results show that the proportion of soluble alpha-synuclein aggregates can distinguish between Parkinson's disease patients and control groups, with Parkinson's disease patients having a higher proportion of larger and rounder alpha-synuclein aggregates. By combining the number and morphology of the aggregates, a new biomarker with improved accuracy for early Parkinson's disease diagnosis was constructed.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Fiamma A. Buratti, Claudio Oscar Fernandez, Markus Zweckstetter
Summary: Parkinson's disease can be either sporadic or inherited, with missense mutations causing the inherited form. The V15A mutation of alpha-synuclein weakens its affinity for membranes but does not significantly affect its conformation in solution. This leads to increased concentration of aggregation-prone alpha-synuclein, allowing the V15A variant to form amyloid fibrils. These findings underscore the importance of maintaining a balance between membrane-bound and free aggregation-competent alpha-synuclein in synucleinopathies.
Article
Chemistry, Multidisciplinary
Shengnan Zhang, Juan Li, Qianhui Xu, Wencheng Xia, Youqi Tao, Chaowei Shi, Dan Li, ShengQi Xiang, Cong Liu
Summary: Many amyloid fibrils associated with neurodegenerative diseases consist of an ordered fibril core and disordered terminal regions. In this study, we used solid-state NMR and cryo-EM techniques to explore the intact structure of an alpha-syn fibril and studied its conformational dynamics upon binding to the LAG3 receptor. Our findings reveal the synergistic conformational transition of the intrinsically disordered terminal regions of alpha-syn, shedding light on the role of these regions in regulating amyloid fibril structure and pathology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Biochemistry & Molecular Biology
Abbie T. Rodger, Maryam A. L. Nasser, Wayne G. Carter
Summary: Currently, there are no pharmacological treatments that can completely stop or reverse the progression of Parkinson's Disease (PD). Therefore, there is a need for neuroprotective therapies. This systematic review examines the effectiveness of anti-a-synuclein (a-syn) therapies in preventing PD progression in preclinical models and human clinical trials. The review found that novel preclinical anti-a-syn therapeutics reduced a-syn aggregations and protected against dopaminergic neuronal loss. Completed clinical trials showed significant tolerability and efficacy in reducing a-syn and minimal adverse effects. Overall, this review highlights the potential of anti-a-syn therapies in both preclinical and clinical settings to reduce a-syn accumulation and potentially slow down PD progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Geriatrics & Gerontology
Jiajun Han, Yaohua Fan, Peipei Wu, Zifeng Huang, Xinrong Li, Lijun Zhao, Yichun Ji, Meiling Zhu
Summary: Parkinson's disease dementia is a common complication of Parkinson's disease that seriously affects patients' health and quality of life. The complex interplay of iron, alpha-synuclein, tau, beta-amyloid, and oxidative stress plays a pivotal role in the mechanism underlying PDD, leading to neuronal protein accumulation, neuroinflammation, and cell death. GSK3 beta is identified as a potential target for the prevention and treatment of PDD due to its central role in regulating the vicious cycle of molecular interactions.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Sarah E. Sandler, Robert I. Horne, Sara Rocchetti, Robert Novak, Nai-Shu Hsu, Marta Castellana Cruz, Z. Faidon Brotzakis, Rebecca C. Gregory, Sean Chia, Goncalo J. L. Bernardes, Ulrich F. Keyser, Michele Vendruscolo
Summary: This study presents a single-molecule approach using solid-state nanopores and multiplexed DNA barcoding for the detection and quantification of protein oligomers. By studying alpha-synuclein oligomers and inhibitors of alpha-synuclein aggregation, the potential applicability of this method to the development of diagnostic and therapeutic methods for Parkinson's disease is demonstrated.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Clinical Neurology
Jia-Li Pu, Chong-Yao Jin, Zhong-Xuan Wang, Yi Fang, Yao-Lin Li, Nai-Jia Xue, Ran Zheng, Zhi-Hao Lin, Yi-Qun Yan, Xiao-Li Si, Ying Chen, Yi Liu, Zhe Song, Ya-Ping Yan, Jun Tian, Xin-Zhen Yin, Bao-Rong Zhang
Summary: The study indicates that patients with Parkinson's disease who carry the APOE ε4 allele may experience faster motor progression, especially in those with high amyloid beta burden. This suggests a potential link between APOE ε4 and rapid motor decline in PD.
MOVEMENT DISORDERS
(2022)
Article
Biochemistry & Molecular Biology
Erwan Bezard
Summary: This opinion paper addresses the issue of conceptual sloppiness and poor methodological characterization in Parkinson's disease research, emphasizing its negative impact on progress and proposing a remedy.
Article
Clinical Neurology
Daniel Kam Yin Chan, Jack Chen, Ren Fen Chen, Jayesh Parikh, Ying Hua Xu, Peter A. Silburn, George D. Mellick
Summary: This study explores the relationship between plasma biomarkers and Mini-Mental State Examination (MMSE) score in Parkinson's disease (PD) patients, finding that alpha-synuclein/A beta 40 and other biomarkers are highly predictive of cognitive impairment and strongly correlated with MMSE score in PD patients compared to controls.
JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Alberto J. Espay, David-Erick Lafontant, Kathleen L. Poston, Chelsea Caspell-Garcia, Luca Marsili, Hyunkeun Ryan Cho, Colin McDaniel, Nessa Kim, Christopher S. Coffey, Abhimanyu Mahajan, Kariem Ezzat, Andrea Sturchio
Summary: This study found that reduction in soluble A beta 42 is associated with lower total brain volume in Parkinson's disease, while changes in brain volume were not associated with levels of other CSF biomarkers.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Clinical Neurology
Evgeniia Lobanova, Daniel Whiten, Francesco S. Ruggeri, Christopher G. Taylor, Antonina Kouli, Zengjie Xia, Derya Emin, Yu P. Zhang, Jeff Y. L. Lam, Caroline H. Williams-Gray, David Klenerman
Summary: The aggregation of alpha-synuclein is important in the development of Parkinson's disease. Studying the aggregates in biofluids such as cerebrospinal fluid (CSF) and serum can provide insights into disease mechanisms and potential diagnostic markers.
Article
Medicine, General & Internal
G. Pagano, K. I. Taylor, J. Anzures-Cabrera, M. Marchesi, T. Simuni, K. Marek, R. B. Postuma, N. Pavese, F. Stocchi, J. -P. Azulay, B. Mollenhauer, L. Lopez-Manzanares, D. S. Russell, J. T. Boyd, A. P. Nicholas, M. R. Luquin, R. A. Hauser, T. Gasser, W. Poewe, B. Ricci, A. Boulay, A. Vogt, F. G. Boess, J. Dukart, G. D'Urso, R. Finch, S. Zanigni, A. Monnet, N. Pross, A. Hahn, H. Svoboda, M. Britschgi, F. Lipsmeier, E. Volkova-Volkmar, M. Lindemann, S. Dziadek, S. Holiga, D. Rukina, T. Kustermann, G. A. Kerchner, P. Fontoura, D. Umbricht, R. Doody, T. Nikolcheva, A. Bonni
Summary: The study found that prasinezumab had no meaningful effect on global or imaging measures of Parkinson's disease progression and was associated with infusion reactions.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Shreyans Chordia, Siddarth Narasimhan, Alessandra Lucini Paioni, Marc Baldus, Gerard Roelfes
Summary: The study demonstrates the supramolecular assembly of ArMs in E. coli cells and their application in enzyme catalysis. Improved mutants were obtained through directed evolution, and the whole-cell ArM system showed catalytic activity without the need for engineering.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Medicine, Research & Experimental
Mahsa Bagheri, Marcel H. Fens, Tony G. Kleijn, Robin B. Capomaccio, Dora Mehn, Przemek M. Krawczyk, Enzo M. Scutigliani, Andrei Gurinov, Marc Baldus, Nicky C. H. van Kronenburg, Robbert J. Kok, Michal Heger, Comelus F. van Nostrum, Wim E. Hennink
Summary: Curcumin-loaded polymeric micelles showed good performance in internalization and prolonged circulation, but no cytostatic effect was observed in neuroblastoma-bearing mice.
MOLECULAR PHARMACEUTICS
(2021)
Article
Biochemical Research Methods
Siddarth Narasimhan, Cecilia Pinto, Alessandra Lucini Paioni, Johan van der Zwan, Gert E. Folkers, Marc Baldus
Summary: Solid-state nuclear magnetic resonance (ssNMR) has been widely used to study complex biomolecular systems. This protocol outlines a biochemical preparation scheme for obtaining cellular samples of soluble and insoluble or membrane-associated proteins, suitable for studying a protein of interest in both whole cells and in cell envelope or isolated membrane preparations.
Article
Biochemistry & Molecular Biology
Anna S. Koenig, Nadine S. Roesener, Lothar Gremer, Markus Tusche, Daniel Flender, Elke Reinartz, Wolfgang Hoyer, Philipp Neudecker, Dieter Willbold, Henrike Heise
Summary: In this study, the researchers used huPrP to preserve and bind Aβ oligomers into large heteroassemblies, and investigated the conformations of Aβ(1-42) oligomers and huPrP complex using solid-state MAS NMR spectroscopy. They found that the Aβ oligomers within the complex exhibit diverse β-strand content, and not all molecules have identical conformations.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Dieter Willbold, Birgit Strodel, Gunnar F. Schroeder, Wolfgang Hoyer, Henrike Heise
Summary: This review focuses on the process of amyloid-type protein aggregation, discussing structures obtained from in vitro and ex vivo studies as well as a model for fibril formation. The model suggests a prion-like nature of all amyloid assemblies, but applying it to the in vivo situation remains complex and raises many unresolved issues.
Article
Multidisciplinary Sciences
Kevin Herr, Max Fleckenstein, Martin Brodrecht, Mark Hoefler, Henrike Heise, Fabien Aussenac, Torsten Gutmann, Michael Reggelin, Gerd Buntkowsky
Summary: A novel spin-labeling strategy is presented for introducing radical spin labels into biomolecules, allowing for structural investigations using EPR and DNP techniques. This strategy successfully introduces spin labels without compromising the overall structure of biomolecules, demonstrating high research potential.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Multidisciplinary
ShengQi Xiang, Cecilia Pinto, Marc Baldus
Summary: Membrane proteins play important biological roles by forming complexes in cell membranes. This study focuses on understanding the role of the lipoprotein BamC in the assembly of the beta-barrel assembly machinery (BAM) complex in lipid bilayers. By developing a selective preparation scheme and using proton-detected solid-state NMR methods, the researchers were able to investigate the structure and dynamics of BamC embedded in the entire BAM complex in lipid bilayers. This approach provides insights into the formation and functioning of membrane protein complexes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Materials Science, Paper & Wood
Lorenz Roesler, Mark Hoefler, Hergen Breitzke, Till Wissel, Kevin Herr, Henrike Heise, Torsten Gutmann, Gerd Buntkowsky
Summary: A novel and efficient approach was developed for the functionalization of microcrystalline cellulose (MCC) in order to immobilize chiral dirhodium catalysts for asymmetric cyclopropanation reactions. The modified cellulose material showed excellent stability and good separation characteristics. The produced catalyst demonstrated high enantioselectivity and recyclability in the cyclopropanation reaction.
Editorial Material
Chemistry, Physical
Marc Baldus, Bert M. Weckhuysen
Summary: This study demonstrates the importance of oxygenates in regulating the conversion of synthesis gas over an oxide-zeolite-based bifunctional catalyst material through advanced solid-state nuclear magnetic resonance experiments.
Article
Chemistry, Multidisciplinary
Adil Safeer, Fleur Kleijburg, Salima Bahri, David Beriashvili, Edwin J. A. Veldhuizen, Jacq van Neer, Martin Tegelaar, Hans de Cock, Han A. B. Wosten, Marc Baldus
Summary: This article demonstrates the application of solid-state NMR spectroscopy in characterizing the composition and structure of the cell wall of Schizophyllum commune. The study reveals the binding preferences of Cu(II) ions, the antifungal peptide Cathelicidin-2, and glucans to cell wall proteins at different concentrations. The presence of polysaccharides containing N-acetyl galactosamine and hydrophobin proteins SC3 is also discovered, providing insights into the molecular make-up and arrangement of cell walls.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Laura M. de Kort, Oscar E. Brandt E. Corstius, Valerio Gulino, Andrei Gurinov, Marc Baldus, Peter Ngene
Summary: Sodium-based complex hydrides have gained attention as electrolytes for all-solid-state batteries due to their light weight and high electrochemical stability. Nanocomposite formation with metal oxides has been found to enhance the ionic conductivity, not only due to the formation of a space charge layer but also as a result of interface reactions between the metal hydrides and oxides. Detailed structural characterization reveals that the disparity in conductivity originates from the formation of different tertiary interfacial compounds. These findings provide insights for the preparation of highly conductive nanocomposite electrolytes by optimizing interface interactions.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Nina Becker, Benedikt Frieg, Lothar Gremer, Tatsiana Kupreichyk, Luis Gardon, Patrick Freiburg, Philipp Neudecker, Dieter Willbold, Holger Gohlke, Henrike Heise
Summary: Alzheimer's disease is associated with the deposition of misfolded aggregates of the amyloid-fi protein (Afi). The study found that relatively homogeneous Afi(1-42) fibrils can be obtained at acidic pH, and the stability and structure of these fibrils are affected by a pH shift. Through various techniques, it was demonstrated that the LS-fold of the Afi(1-42) fibrils remains stable at physiological pH values, with the N-terminus being part of the fibril core.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Robert Pylkkanen, Daniel Werner, Ajit Bishoyi, Dominik Weil, Ernesto Scoppola, Wolfgang Wagermaier, Adil Safeer, Salima Bahri, Marc Baldus, Arja Paananen, Merja Penttila, Geza R. Szilvay, Pezhman Mohammadi
Summary: We demonstrate that Fomes fomentarius is a unique material with exceptional mechanical properties due to its structural design. It consists of three distinct layers with different microstructures and adhesive properties, resulting in its high strength and toughness.
Article
Chemistry, Multidisciplinary
Nina Becker, Benedikt Frieg, Lothar Gremer, Tatsiana Kupreichyk, Luis Gardon, Patrick Freiburg, Philipp Neudecker, Dieter Willbold, Holger Gohlke, Henrike Heise
Summary: Alzheimer's disease is characterized by the accumulation of misfolded amyloid-fi protein (Afi). We found that Afi(1-42) fibrils with a predominant fold can be obtained at acidic pH, and their structure differs from polymorphs obtained at neutral pH.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Ru Yao, David Beriashvili, Wenxiao Zhang, Shuai Li, Adil Safeer, Andrei Gurinov, Antal Rockenbauer, Yin Yang, Yuguang Song, Marc Baldus, Yangping Liu
Summary: Cellular dynamic nuclear polarization is an effective method for overcoming the sensitivity limitations of solid-state nuclear magnetic resonance spectroscopy, allowing atomic-level characterization of biomolecules in their native environments. Researchers have synthesized a highly bioresistant and hydrophilic polarizing agent, StaPol-1, which shows excellent performance in reductive environments and is suitable for DNP ssNMR investigations at high magnetic fields.
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)
