Article
Biochemistry & Molecular Biology
Daniel Oppermann Peixoto, Reykla Ramon Bittencourt, Juciano Gasparotto, Flavio Gabriel Carazza Kessler, Pedro Ozorio Brum, Nauana Somensi, Carolina Saibro Girardi, Lucas dos Santos da Silva, Tiago Fleming Outeiro, Jose Claudio Fonseca Moreira, Daniel Pens Gelain
Summary: This study investigates the effects of RAGE inhibition in the brain using an antagonist FPS-ZM1, and suggests that blocking encephalic RAGE can attenuate chronic neuroinflammation and potentially be a therapeutic approach for conditions such as Parkinson's disease.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Alina A. Sofronova, Denis V. Pozdyshev, Kseniya V. Barinova, Vladimir I. Muronetz, Pavel I. Semenyuk
Summary: The study found that glycation of GAPDH inhibits its interaction with alpha-synuclein and RNA, potentially influencing the interplay between diabetes and neurodegenerative diseases.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Ana Belen Uceda, Juan Frau, Bartolome Vilanova, Miquel Adrover
Summary: Parkinson's disease is a prevalent neurodegenerative disorder characterized by the accumulation of insoluble Lewy bodies in neurons, leading to neuronal death. The main component of these Lewy bodies, alpha-synuclein, undergoes non-enzymatic post-translational modifications, which affect its aggregation and physiological function. Understanding these modifications is crucial for better understanding the mechanisms underlying diabetes-induced Parkinson's disease.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Qiong-Qiong Yao, Jitao Wen, Sarah Perrett, Si Wu
Summary: This study reveals the mechanisms by which lipid membranes influence the amyloid formation of Tau protein. It shows that lipid membranes can induce conformational changes in Tau and either accelerate or inhibit its fibrillation process depending on the concentration of the lipid membrane.
Article
Biophysics
Istvan Horvath, Ranjeet Kumar, Pernilla Wittung-Stafshede
Summary: The presence of macromolecular crowding agent Ficoll70 accelerates primary nucleation and fiber elongation steps during alpha-synuclein amyloid formation, favoring secondary nucleation and resulting in faster overall reaction. In contrast, sucrose slows down alpha-synuclein amyloid formation. The ability of cell environments to modulate reaction kinetics, such as accelerating individual steps in alpha-synuclein amyloid formation, is a crucial consideration for biochemical reactions in living systems.
BIOPHYSICAL JOURNAL
(2021)
Article
Chemistry, Physical
Jessica S. Fortin, Kazuma Shimanaka, A. Prasanth Saraswati, Mengyu Liu, Kuan-Wei Wang, Hsiao-Tien Hagar, Soham Maity, Susantha K. Ganegamage, Edmund Ellsworth, Scott E. Counts, Babak Borhan, Ulf Dettmer, Min-Hao Kuo
Summary: Contrary to A n plaques, the distribution of hyperphosphorylated tau (p-tau) neurofibrillary tangles predicts cognitive impairment in Alzheimer's disease (AD). This underscores the importance of controlling p-tau aggregation and cytotoxicity in AD therapeutics. A drug discovery program focusing on the tau isoform 1N4R has developed compounds that prevent p-tau aggregation and cytotoxicity. Among the tested small molecules, sulfonamide derivatives 18 and 20 showed anti-aggregation activity on alpha-synuclein and p-tau, reducing inclusion formation in neuroblastoma cells. This project introduces new concepts in targeting prone-to-aggregate proteins and provides a molecular scaffold for AD drug development.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
News Item
Chemistry, Multidisciplinary
Sheena E. Radford, Theodoros K. Karamanos
Summary: Research has revealed the significant impact of O-GlcNAcylation on chaperone activity and inhibition of amyloid fibril formation, potentially offering new avenues for combating neurodegenerative diseases.
Article
Biochemistry & Molecular Biology
Rita Rosado-Ramos, Joana Godinho-Pereira, Daniela Marques, Ines Figueira, Tiago Fleming Outeiro, Regina Menezes, Claudia Nunes dos Santos
Summary: The study found that fisetin has neuroprotective effects and modulates cellular pathologies related to Parkinson's Disease, reducing the formation of PD hallmark inclusions and increasing dopamine transporter levels.
Article
Chemistry, Multidisciplinary
Afshan Iqbal, Fareeha Anwar, Uzma Saleem, Saira Sami Khan, Adnan Karim, Bashir Ahmad, Mubashra Gul, Zafer Iqbal, Tariq Ismail
Summary: This study found that Toco-D may be effective in improving locomotor activity and motor coordination in haloperidol-induced Parkinson's disease. Toco-D increased antioxidant enzyme and neurotransmitter levels, while decreasing inflammatory cytokine levels and mRNA expression of alpha-synuclein.
Article
Neurosciences
Ana Chegao, Mariana Guarda, Bruno M. Alexandre, Liana Shvachiy, Mariana Temido-Ferreira, Ines Marques-Morgado, Barbara Fernandes Gomes, Rune Matthiesen, Luisa V. Lopes, Pedro R. Florindo, Ricardo A. Gomes, Patricia Gomes-Alves, Joana E. Coelho, Tiago Fleming Outeiro, Hugo Vicente Miranda
Summary: This study found that MGO-induced glycation accelerates PD-like sensorimotor and cognitive alterations and increases the accumulation of α-synuclein in the brain. In addition, the study also found that MGO mainly affects glutamatergic signaling in the midbrain, which may be associated with PD and dopaminergic pathways.
NPJ PARKINSONS DISEASE
(2022)
Article
Immunology
Adrianne F. Pike, Francesca Longhena, Gaia Faustini, Jean-Marc Van Eik, Iris Gombert, Maaike A. C. Herrebout, Mona M. H. E. Fayed, Michele Sandre, Tatiana Varanita, Charlotte E. Teunissen, Jeroen J. M. Hoozemans, Arianna Bellucci, Robert Veerhuis, Luigi Bubacco
Summary: This study reveals that dopamine inhibits the activation of NLRP3 inflammasome in primary human microglia, providing insights into the potential therapeutic target for Parkinson's disease.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Xiaoguang Liu, Kaluvu Balaraman, Ciaran C. Lynch, Michaeline Hebron, Priya Ketankumar Shah, Shicheng Hu, Max Stevenson, Christian Wolf, Charbel Moussa
Summary: The study found that Ubiquitin-Specific Protease-13 (USP13) plays a critical role in the neuropathology of alpha-synuclein and inhibiting USP13 can reduce alpha-synuclein levels and improve motor and behavioral symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Depeng Yang, Lijun Yang, Jialing Cai, Xibo Hu, Huaxin Li, Xiaoqing Zhang, Xiaohan Zhang, Xinghe Chen, Haiyang Dong, Huan Nie, Yu Li
Summary: Macrophages are functionally plastic cells that regulate immunity and inflammatory responses by producing various bioactive molecules. They can adopt different phenotypes in response to signals, and glycobiology is closely associated with this process.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Maria Babu, Filippo Favretto, Marija Rankovic, Markus Zweckstetter
Summary: The study reveals that peptidyl prolyl isomerases play a regulatory role in the liquid-liquid phase separation of proline-rich intrinsically disordered proteins. These isomerases concentrate inside the liquid droplets formed by the proteins and trigger their dissolution, leading to the return of a single mixed phase.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Neurosciences
Daniel Pens Gelain, Reykla Ramon Bittencourt, Luiz Filipe Bastos Mendes, Jose Claudio Fonseca Moreira, Tiago Fleming Outeiro
Summary: Oligomerization and aggregation of misfolded alpha-synuclein are important mechanisms in PD and synucleinopathies. Glycation as a post-translational modification can impact the aggregation, toxicity, and clearance of alpha-synuclein. The receptor for advanced glycation end products (RAGE) is involved in neuroinflammation in PD, although there are conflicting findings on its expression and interaction with alpha-synuclein.
JOURNAL OF PARKINSONS DISEASE
(2023)
Article
Chemistry, Multidisciplinary
Hossein Mohammad-Beigi, Masumeh Zanganeh, Carsten Scavenius, Hoda Eskandari, Azad Farzadfard, Seyed Abbas Shojaosadati, Jan J. Enghild, Daniel E. Otzen, Alexander K. Buell, Duncan S. Sutherland
Summary: Nanoparticles can modulate protein aggregation and fibril formation in amyloid diseases. By attaching a protein corona to the nanoparticles, the interactions between alpha-Synuclein and the nanoparticles were studied. The results showed that the nanoparticles surface promotes the primary nucleation step of fibril formation and that the protein corona reduces the accelerating effect of the nanoparticles.
Article
Immunology
Kristian Stodkilde, Jakob Toudahl Nielsen, Steen Vang Petersen, Bernhard Paetzold, Holger Bruggemann, Frans A. A. Mulder, Christian Brix Folsted Andersen
Summary: Cutibacterium acnes is a bacterium commonly found on human skin, and its secreted protein RoxP has been shown to have antioxidant activity and can alleviate cell damage caused by radicals. The structure of RoxP reveals a positively charged groove that may function as a binding site for cofactors or substrates. It is not responsible for the adhesion of C. acnes bacteria to human keratinocytes, but the antioxidant activity of RoxP is likely attributed to tyrosine-containing stretches located in its flexible loop.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jasmin Bartl, Marco Zanini, Flavia Bernardi, Antoine Forget, Lena Bluemel, Julie Talbot, Daniel Picard, Nan Qin, Gabriele Cancila, Qingsong Gao, Soumav Nath, Idriss Mahoungou Koumba, Marietta Wolter, Francois Kuonen, Maike Langini, Thomas Beez, Christopher Munoz, David Pauck, Viktoria Marquardt, Hua Yu, Judith Souphron, Mascha Korsch, Christina Moelders, Daniel Berger, Sarah Goebbels, Frauke-Dorothee Meyer, Bjorn Scheffler, Barak Rotblat, Sven Diederichs, Vijay Ramaswamy, Hiromishi Suzuki, Anthony Oro, Kai Stuehler, Anja Stefanski, Ute Fischer, Gabriel Leprivier, Dieter Willbold, Gerhard Steger, Alexander Buell, Marcel Kool, Peter Lichter, Stefan M. Pfister, Paul A. Northcott, Michael D. Taylor, Arndt Borkhardt, Guido Reifenberger, Olivier Ayrault, Marc Remke
Summary: Long non-coding RNA (lncRNA) HHIP-AS1 stabilizes the mRNA of dynein complex 1, thereby promoting the pro-mitotic effects of SHH-driven tumors.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Henrik Pedersen, Rasmus Kjeldsen Jensen, Annette Gudmann Hansen, Steen Vang Petersen, Steffen Thiel, Nick Stub Laursen, Gregers Rom Andersen
Summary: The complement system plays a role in labeling pathogens and dying host cells for clearance. A nanobody has been discovered that specifically binds to degradation products of complement component C3 and effectively inhibits complement deposition. This nanobody could be a potential candidate for studying complement-related diseases in rodent models.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Ye Zhou, Jannik Nedergaard Pedersen, Jacob Nedergaard Pedersen, Nykola C. Jones, Soren Vronning Hoffmann, Steen Vang Petersen, Jan Skov Pedersen, Adam Perriman, Renjun Gao, Zheng Guo
Summary: This study focuses on the anionization of a carboxylate-enriched mutant of Bacillus subtilis lipase A (8M) to produce biofluids with enhanced hydrolytic activity. The resulting biofluids show a 2.5-fold increase in activity compared to those based on anionic polymer surfactants. Additionally, the use of anion-type biofluids with Myoglobin (Mb) is evaluated, revealing partial recovery of the active alpha-helix level in the biofluids. These highly active solvent-free liquid enzymes exhibit increased thermal stability and open up new possibilities in solvent-free liquid protein research.
Article
Biology
Rebecca Sternke-Hoffmann, Thomas Pauly, Rasmus K. Norrild, Jan Hansen, Florian Tucholski, Magnus Haraldson Hoie, Paolo Marcatili, Mathieu Dupre, Magalie Duchateau, Martial Rey, Christian Malosse, Sabine Metzger, Amelie Boquoi, Florian Platten, Stefan U. Egelhaaf, Julia Chamot-Rooke, Roland Fenk, Luitgard Nagel-Steger, Rainer Haas, Alexander K. Buell
Summary: Researchers introduce a new systematic workflow for the biophysical characterization of multiple myeloma patient-derived immunoglobulin light chains (IgLCs) and find that in vivo aggregation behavior is unlikely to be linked to any single biophysical or biochemical parameter. They also discover that the potential to form amyloid fibrils is widespread in IgLC sequences and not limited to those sequences that form fibrils in patients.
Article
Medicine, Research & Experimental
Andreas V. Madsen, Peter Kristensen, Alexander K. Buell, Steffen Goletz
Summary: This study demonstrates a simple and efficient method to generate high-quality bsAbs with both binding functionalities intact by fusing sdAbs onto IgG scaffolds through flexible linkers. By systematically comparing sdAb fusion strategies, the results show that fusion of sdAbs to the heavy chain promotes good expression, stability, and efficient binding to both antigens. The study also provides a toolbox of complementary methods for in-depth analysis of key features, such as dual antigen binding and stability, to ensure high bsAb quality.
Article
Chemistry, Multidisciplinary
Soumik Ray, Thomas O. Mason, Lars Boyens-Thiele, Azad Farzadfard, Jacob Aunstrup Larsen, Rasmus K. Norrild, Nadin Jahnke, Alexander K. Buell
Summary: Using mass photometry, it is shown that the Parkinson's disease-related protein, α-synuclein, can form dynamic nanoscale clusters and promote amyloid fibril formation. The formation of these nanoclusters is instantaneous and occurs at much wider ranges of solution conditions. Mass photometry is demonstrated to be a promising methodology for detecting and quantifying nanoscale precursors of phase separation.
Article
Biochemistry & Molecular Biology
Jayakrishna Shenoy, Alons Lends, Melanie Berbon, Muhammed Bilal, Nadia El Mammeri, Mathilde Bertoni, Ahmad Saad, Estelle Morvan, Axelle Grelard, Sophie Lecomte, Francois-Xavier Theillet, Alexander K. Buell, Brice Kauffmann, Birgit Habenstein, Antoine Loquet
Summary: Aberrant aggregation of TDP-43 protein is linked to lethal neurodegenerative diseases. Using a combination of techniques, we found that different fragments of TDP-43 adopt distinct polymorphic structures in their amyloid fibrillar state. Our study reveals that removal of a small portion of the low-complexity sequence can lead to amyloid fibrils with similar macroscopic features but different local structural arrangements.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Christian E. Rusbjerg-Weberskov, Mette Liere Johansen, Jan S. Nowak, Daniel E. Otzen, Jan Skov Pedersen, Jan J. Enghild, Nadia Sukusu Nielsen
Summary: Human periostin is a matricellular protein that plays important roles in extracellular matrix remodeling, tumor development, and inflammatory diseases. The C-terminal domain of periostin interacts with other domains and proteins, potentially contributing to the pathogenesis of diseases such as atopic dermatitis.
Review
Chemistry, Physical
Marcos Lopez Hernandez, Jan Skov Pedersen, Daniel E. Otzen
Summary: The synergies between surfactants and proteins are widely utilized in various fields, but there is still room for improvement in terms of sustainability. Biosurfactants offer an attractive alternative, and understanding their interactions with proteins can open up new opportunities. This review focuses on the self-assembly of protein:BS complexes and the effects of BS on enzymatic activity.
CURRENT OPINION IN COLLOID & INTERFACE SCIENCE
(2023)
Article
Multidisciplinary Sciences
Steven J. Roeters, Kris Strunge, Kasper B. Pedersen, Thaddeus W. Golbek, Mikkel Bregnhoj, Yuge Zhang, Yin Wang, Mingdong Dong, Janni Nielsen, Daniel E. Otzen, Birgit Schiott, Tobias Weidner
Summary: This study reports a mechanism explaining why lipid membranes catalyze the formation of harmful aggregates at elevated concentrations.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Soumav Nath, Alexander K. Buell, Bogdan Barz
Summary: The aggregation of amyloid beta (Aβ) peptide is a major hallmark of Alzheimer's disease. Different forms of Aβ peptide in amyloid plaques have distinct biophysical and biochemical properties, with N-terminally pyroglutamate-modified variant pE-Aβ(3-42) being a significant fraction in AD brains. Molecular dynamics simulations reveal significant differences in the structural flexibility, secondary structure, and hydrophobic exposure between pE-Aβ(3-42) monomer and Aβ(1-42) monomer, which might contribute to their different behavior in biophysical experiments.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)