Article
Biochemistry & Molecular Biology
Antoine Canat, Derya Atilla, Maria-Elena Torres-Padilla
Summary: This study investigates the impact of mechanical stress on the reprogramming of mouse embryonic stem cells (ESCs) to 2-cell-like cells (2CLCs). The results show that hyperosmotic stress can induce the formation of 2CLCs, and this induction can occur even after a recovery time from the stress, suggesting a memory response. Hyperosmotic stress in ESCs leads to the accumulation of reactive-oxygen species (ROS) and activation of the ATR checkpoint, both of which are essential for the induction of 2CLCs. These findings shed light on the response of ESCs to mechanical stress and provide insights into the reprogramming of 2CLCs.
Review
Biochemistry & Molecular Biology
Jennifer Ramirez, Samantha X. Pancoe, Elizabeth Rhoades, E. James Petersson
Summary: This article investigates the effects of interactions between the small neuronal protein alpha-synuclein and lipids on aggregation. By analyzing a comprehensive collection of experimental data, the general trends of lipid structure influencing aggregation are identified, providing a resource for interpreting the effects of lipids on aggregation and potentially serving as inputs for computational models.
Article
Biochemistry & Molecular Biology
Marco Greco, Chiara Carmela Spinelli, Lidia De Riccardis, Alessandro Buccolieri, Simona Di Giulio, Debora Musaro, Claudia Pagano, Daniela Manno, Michele Maffia
Summary: Copper dysregulation is linked to various neuropathologies such as Parkinson's disease; differentiated neurons express higher levels of CTR1 protein leading to increased copper uptake; copper treatment enhances phosphorylation of alpha-synuclein, potentially offering new opportunities for clinical intervention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
Neurosciences
Savannah M. Rocha, Collin M. Bantle, Tawfik Aboellail, Debotri Chatterjee, Richard J. Smeyne, Ronald B. Tjalkens
Summary: This study establishes a reproducible murine model of rotenone-induced Parkinson's disease and explores the effects of rotenone exposure on neuroinflammation, protein aggregation, and loss of dopaminergic neurons. The results indicate that rotenone exposure leads to progressive accumulation and regional spread of p129 aggregates, which precede the maximal loss of dopaminergic neurons. The activation of glial cells and aggregation of p129 appear to be driving factors in neurodegeneration following rotenone-induced neurotoxic stress.
NEUROBIOLOGY OF DISEASE
(2022)
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
Irena Hlushchuk, Justyna Barut, Mikko Airavaara, Kelvin Luk, Andrii Domanskyi, Piotr Chmielarz
Summary: This study is the first attempt to investigate the direct effects of insulin signaling on pathological alpha-synuclein accumulation in dopamine neurons. The results suggest that modifying insulin signaling does not significantly affect alpha-synuclein aggregation, but the choice of culturing media can significantly affect preformed fibril-induced alpha-synuclein phosphorylation in dopamine neurons.
Article
Neurosciences
Hao Gu, Xiuli Yang, Xiaobo Mao, Enquan Xu, Chen Qi, Haibo Wang, Saurav Brahmachari, Bethany York, Manjari Sriparna, Amanda Li, Michael Chang, Pavan Patel, Valina L. Dawson, Ted M. Dawson
Summary: The depletion of Lag3 in transgenic mice carrying human alpha-syn A53T mutation significantly reduces insoluble alpha-syn aggregates, delays disease progression, improves behavioral deficits, and prolongs survival, indicating the contribution of Lag3 to the pathogenesis in this model.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Pharmacology & Pharmacy
Md Ezazul Haque, Mahbuba Akther, Shofiul Azam, In-Su Kim, Yuxi Lin, Young-Ho Lee, Dong-Kug Choi
Summary: In Parkinson's disease, the aggregated alpha-synuclein in Lewy bodies and mitochondrial dysfunction play crucial roles in neurodegeneration, with interactions between aggregated alpha-synuclein and mitochondria potentially leading to neuronal loss, making it an emerging drug target for Parkinson's disease treatment.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Eva M. Szego, Chris van den Haute, Lennart Hofs, Veerle Baekelandt, Anke van der Perren, Bjorn H. Falkenburger
Summary: This study found that stimulating the autolysosomal degradation through the Rab7 pathway can reduce cellular impairments induced by alpha Syn and prevent neurodegeneration in PD.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Seo-Jun Kang, Soo-Jeong Kim, Hye Rin Noh, Beom Jin Kim, Jae-Bong Kim, Uram Jin, Sun Ah Park, Sang Myun Park
Summary: In this study, the role of neuronal ApoE in the cell-to-cell transmission of alpha-synuclein (alpha-syn) was evaluated. It was found that ApoE deficiency attenuates alpha-syn uptake and release, thereby contributing to its propagation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Rose B. Creed, Adeel A. Memon, Sindhu P. Komaragiri, Sandeep K. Barodia, Matthew S. Goldberg
Summary: The study suggests that intrastriatal injection of mice with small length PFFs induces extensive bilateral protein aggregates, significant unilateral nigral cell loss, and altered levels of mitochondrial proteins and respiratory chain activity, offering insights into the role of mitochondrial dysfunction in alpha-synucleinopathies and potential for testing neuroprotective therapies.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
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
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
Biochemistry & Molecular Biology
R. Kavya, Snehal Aouti, Sneha Jos, Thazhe Kootteri Prasad, K. N. Kumuda, Sruthi Unni, Balasundaram Padmanabhan, Neelagandan Kamariah, Sivaraman Padavattan, Rajeswara Babu Mythri
Summary: Alpha-synuclein aggregation, associated with Parkinson's disease, is driven by the region alpha Syn(36-42) and alpha Syn(1-12). Celastrol, one of the screened phytochemicals, exhibits high binding affinity with alpha Syn. NMR analysis confirms stable interactions between alpha Syn and celastrol, reducing alpha Syn aggregation, making celastrol a potential drug candidate for Parkinson's disease.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Biochemistry & Molecular Biology
Maria Andreasen, Nikolai Lorenzen, Daniel Otzen
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2015)
Article
Biophysics
Natalia V. Kulminskaya, Yuichi Yoshimura, Kasper Runager, Charlotte S. Sorensen, Morten Bjerring, Maria Andreasen, Daniel E. Otzen, Jan J. Enghild, Niels Chr. Nielsen, Frans A. A. Mulder
BIOMOLECULAR NMR ASSIGNMENTS
(2016)
Article
Biochemistry & Molecular Biology
Marcel Stenvang, Nicholas P. Schafer, Kirsten Gade Malmos, Adriana-Michelle Wolf Perez, Olatz Niembro, Pietro Sormanni, Rajiv Vaid Basaiawmoit, Gunna Christiansen, Maria Andreasen, Daniel E. Otzen
JOURNAL OF MOLECULAR BIOLOGY
(2018)
Article
Multidisciplinary Sciences
Jonathan D. Taylor, William J. Hawthorne, Joanne Lo, Alexander Dear, Neha Jain, Georg Meisl, Maria Andreasen, Catherine Fletcher, Marion Koch, Nicholas Darvill, Nicola Scull, Andres Escalera-Maurer, Lea Sefer, Rosemary Wenman, Sebastian Lambert, Jisoo Jean, Yingqi Xu, Benjamin Turner, Sergei G. Kazarian, Matthew R. Chapman, Doryen Bubeck, Alfonso de Simone, Tuomas P. J. Knowles, Steve J. Matthews
SCIENTIFIC REPORTS
(2016)
Article
Biochemistry & Molecular Biology
Casper B. Rasmussen, Gunna Christiansen, Brian S. Vad, Carina Lynggaard, Jan J. Enghild, Maria Andreasen, Daniel Otzen
Article
Microbiology
Maria Andreasen, Georg Meisl, Jonathan D. Taylor, Thomas C. T. Michaels, Aviad Levin, Daniel E. Otzen, Matthew R. Chapman, Christopher M. Dobson, Steve J. Matthews, Tuomas P. J. Knowles
Article
Polymer Science
Xizhou Liu, Zenon Toprakcioglu, Alexanderj Dear, Aviad Levin, Francesco Simone Ruggeri, Christopher C. Taylor, Mengsha Hu, Anet R. Kumita, Maria Andreasen, Christopher M. Dobson, Ulyana Shimanovich, Tuomas P. J. Knowles
MACROMOLECULAR RAPID COMMUNICATIONS
(2019)
Article
Biology
Masihuz Zaman, Maria Andreasen
Article
Microbiology
Masihuz Zaman, Maria Andreasen
Summary: This study evaluated the effect of different pH values on the formation of functional amyloids of Staphylococcus aureus pathogen PSM peptides, revealing a pH-induced switch in PSM aggregation kinetics. The research suggests that pH can modulate the aggregation properties of these peptides, and different PSMs show varying rates of fibril elongation, indicating no clear correlation between them.
Article
Biochemistry & Molecular Biology
Zahra Najarzadeh, Masihuz Zaman, Vita Sereikaite, Kristian Stromgaard, Maria Andreasen, Daniel E. Otzen
Summary: The study shows that heparin accelerates fibrillation of alpha-PSMs and 8-toxin, but inhibits beta-PSM fibrillation. Heparin provides a scaffold to catalyze or inhibit fibrillation, potentially enhancing bacterial biofilm and colonization through increased PSM fibrillation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Georg Meisl, Catherine K. Xu, Jonathan D. Taylor, Thomas C. T. Michaels, Aviad Levin, Daniel Otzen, David Klenerman, Steve Matthews, Sara Linse, Maria Andreasen, Tuomas P. J. Knowles
Summary: The study reveals that both disease-related proteins and proteins with functional roles in biology are capable of self-replication. However, the rate of self-replication is insignificant on the biologically relevant time scale for proteins fulfilling structural roles, while disease-related proteins can self-replicate quickly within the associated disease's time scale.
Article
Biochemistry & Molecular Biology
Mitra Pirhaghi, Signe Andrea Frank, Parvez Alam, Janni Nielsen, Vita Sereikaite, Arpit Gupta, Kristian Stromgaard, Maria Andreasen, Deepak Sharma, Ali Akbar Saboury, Daniel Erik Otzen
Summary: This study identified nine peptides with high specificity and affinity for α-synuclein oligomers (αSOs) using peptide arrays. Peptides p194, p235, and p249 diverted α-synuclein aggregation from fibrils to amorphous aggregates with reduced II-structures and increased random coil content. In addition, a non-aggregating peptide p216 showed 12-fold higher binding affinity to αSOs than to α-synuclein monomers. These findings suggest that p216 is a promising starting point for developing peptides targeting toxic αSOs in Parkinson's disease.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Umit Akbey, Maria Andreasen
Summary: Functional amyloids play an important structural role in bacterial biofilms and are associated with antibiotic resistance. They interact with components in the extracellular matrix and are linked to disease-related amyloids.
Article
Chemistry, Analytical
Manuela Pfammatter, Maria Andreasen, Georg Meisl, Christopher G. Taylor, Jozef Adamcik, Sreenath Bolisetty, Antoni Sanchez-Ferrer, David Klenerman, Christopher M. Dobson, Raffaele Mezzenga, Tuomas P. J. Knowles, Adriano Aguzzi, Simone Hornemann
ANALYTICAL CHEMISTRY
(2017)