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, 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)
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
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
Biochemistry & Molecular Biology
Pawanrat Chalorak, Tanatcha Sanguanphun, Tanapol Limboonreung, Krai Meemon
Summary: The study demonstrates that saponins from sea cucumber and ginseng have beneficial effects in rescuing dopaminergic neurodegeneration in C. elegans by suppressing apoptosis mediators and stimulating antioxidant enzymes. Additionally, frondoside A from sea cucumber can attenuate alpha-synuclein aggregation through the protein degradation process.
Article
Chemistry, Multidisciplinary
Xidong Li, Qiushi Li, Yanhui Zhang, Yang Bai, Yue Cao, Yang Yang, Lie Zang, Meiyi Huang, Rubo Sui
Summary: This study investigated the effects of NiO NPs on protein aggregation and found that NiO NPs accelerated the formation of α-synuclein amyloids and enhanced their cytotoxicity. Through a series of analyses, the results showed that the interaction between NiO NPs and α-synuclein exacerbated the development of neuroadaptive diseases.
ARABIAN JOURNAL OF CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Yaxian Liu, Xiaoyi Wang, Giulia Campolo, Xiangyu Teng, Liming Ying, Joshua B. Edel, Aleksandar P. Ivanov
Summary: This study develops a strategy that combines nanopore-based sensing with molecular carriers to detect α-Synuclein oligomers directly in clinical samples, providing a new approach for the diagnosis and mechanism study of Parkinson's disease.
Review
Cell Biology
Andrei Surguchov
Summary: Parkinson's disease is the second most common neurodegenerative disease globally, affecting approximately 10 million people. Despite the identification of several genes linked to PD, it remains primarily an idiopathic disorder. Recent studies have shown that various risk factors can accelerate or exacerbate brain dysfunction in PD patients, and research using non-mammalian model organisms may reveal new mechanisms underlying the disease.
Review
Neurosciences
Tiago Fleming Outeiro
Summary: In protein aggregation disorders, oligomeric species may be more toxic than fibrillar forms. Definitive data on the nature of toxic species are lacking due to difficulties in detecting and defining protein aggregate species.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Medicine, General & Internal
E. Srinivasan, G. Chandrasekhar, P. Chandrasekar, K. Anbarasu, A. S. Vickram, Rohini Karunakaran, R. Rajasekaran, P. S. Srikumar
Summary: Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons, with pathogenesis linked to the misfolding and mutations of alpha-synuclein protein. Genetic and other factors lead to the formation of amyloid structures from alpha-synuclein, causing PD.
FRONTIERS IN MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Edward Chau, Jin Ryoun Kim
Summary: This study investigated the interactions between Aβ42 and αS in different conformations. It was found that αS monomers and oligomers promoted the oligomerization and stabilization of soluble Aβ42, while αS fibrils hindered the aggregation of Aβ42. These interactions may be achieved through direct binding or co-assembly, and different parts of Aβ42 mediated the interactions with αS.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(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
Geriatrics & Gerontology
Roman Vozdek, Peter P. Pramstaller, Andrew A. Hicks
Summary: This study established a model of PD in dopaminergic neurons and identified modulators that may represent new potential therapeutic targets for neurodegenerative proteopathies and other aging-related diseases.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Chao Pang, Na Zhang, Mojtaba Falahati
Summary: The study demonstrated that SiO2 NPs can accelerate the formation of α-syn amyloid fibrils and increase their cytotoxicity. Experimental results indicate that SiO2 NPs induce the cytotoxic effects of α-syn amyloid fibrils through the mitochondrial-mediated intrinsic apoptosis pathway.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Cell Biology
Michele Perni, Annemieke van der Goot, Ryan Limbocker, Tjakko J. van Ham, Francesco A. Aprile, Catherine K. Xu, Patrick Flagmeier, Karen Thijssen, Pietro Sormanni, Giuliana Fusco, Serene W. Chen, Pavan K. Challa, Julius B. Kirkegaard, Romain F. Laine, Kai Yu Ma, Martin B. D. Muller, Tessa Sinnige, Janet R. Kumita, Samuel I. A. Cohen, Renee Seinstra, Gabriele S. Kaminski Schierle, Clemens F. Kaminski, Denise Barbut, Alfonso De Simone, Tuomas P. J. Knowles, Michael Zasloff, Ellen A. A. Nollen, Michele Vendruscolo, Christopher M. Dobson
Summary: The aggregation of alpha-synuclein is a key feature of Parkinson's disease, and mutations in this protein are associated with familial forms of the disease. Two C. elegans models expressing mutational variants were studied, showing different behavioral manifestations and levels of aggregation. Squalamine was found to reduce aggregation and toxicity of alpha-synuclein in certain models. Targeting specific regions of alpha-synuclein with antibodies also showed suppression of toxicity in the models. These findings demonstrate the utility of these models in Parkinson's disease research.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Federica Quaglia, Balint Meszaros, Edoardo Salladini, Andras Hatos, Rita Pancsa, Lucia B. Chemes, Matyas Pajkos, Tamas Lazar, Samuel Pena-Diaz, Jaime Santos, Veronika Acs, Nazanin Farahi, Erzsebet Ficho, Maria Cristina Aspromonte, Claudio Bassot, Anastasia Chasapi, Norman E. Davey, Radoslav Davidovic, Laszlo Dobson, Arne Elofsson, Gabor Erdos, Pascale Gaudet, Michelle Giglio, Juliana Glavina, Javier Iserte, Valentin Iglesias, Zsofia Kalman, Matteo Lambrughi, Emanuela Leonardi, Sonia Longhi, Sandra Macedo-Ribeiro, Emiliano Maiani, Julia Marchetti, Cristina Marino-Buslje, Attila Meszaros, Alexander Miguel Monzon, Giovanni Minervini, Suvarna Nadendla, Juliet F. Nilsson, Marian Novotny, Christos A. Ouzounis, Nicolas Palopoli, Elena Papaleo, Pedro Jose Barbosa Pereira, Gabriele Pozzati, Vasilis J. Promponas, Jordi Pujols, Alma Carolina Sanchez Rocha, Martin Salas, Luciana Rodriguez Sawicki, Eva Schad, Aditi Shenoy, Tamas Szaniszlo, Konstantinos D. Tsirigos, Nevena Veljkovic, Gustavo Parisi, Salvador Ventura, Zsuzsanna Dosztanyi, Peter Tompa, Silvio C. E. Tosatto, Damiano Piovesan
Summary: The latest update of DisProt version 9 includes a restyled web interface, refactored IDPO, improvements in curation process, and around 30% content growth. The newly implemented reviewing process and curator training aim to provide higher quality and more consistent annotations. Integration with APICURON and adoption of MIADE standard, along with collaborations with GO and ECO consortia and support from ELIXIR infrastructure, enhance interoperability.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Samuel Pena-Diaz, Jordi Pujols, Eftychia Vasili, Francisca Pinheiro, Jaime Santos, Zoe Manglano-Artunedo, Tiago F. Outeiro, Salvador Ventura
Summary: Parkinson's disease is characterized by the loss of dopaminergic neurons and the accumulation of proteinaceous inclusions. The intrinsically disordered protein alpha-synuclein (alpha-Syn) plays a major role in the formation of these inclusions. In this study, researchers generated different alpha-Syn amyloid conformations and found that a compound called SC-D can reduce aggregation and fibril formation of alpha-Syn. Additionally, SC-D showed activity in disaggregating fibrils and reducing strain-specific intracellular accumulation of phosphorylated alpha-Syn. These findings suggest that SC-D may be a promising compound for inhibiting polymorphic alpha-Syn aggregation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Laura De Luca, Serena Vittorio, Samuel Pena-Diaz, Giovanna Pitasi, Marc Fornt-Sune, Federica Bucolo, Salvador Ventura, Rosaria Gitto
Summary: This study identified a potent α-Syn amyloid formation inhibitor, MeSC-04, through ligand-based virtual screening and investigated its structural requirements. The results demonstrated that MeSC-04 exhibited similar behavior to the known inhibitor SynuClean-D in reducing the number and size of amyloid fibrils. Molecular modeling studies provided insights into the binding mode of MeSC-04 with α-Syn fibrils.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Francisca Pinheiro, Irantzu Pallares, Francesca Peccati, Adria Sanchez-Morales, Nathalia Varejao, Filipa Bezerra, David Ortega-Alarcon, Danilo Gonzalez, Marcelo Osorio, Susanna Navarro, Adrian Velazquez-Campoy, Maria Rosario Almeida, David Reverter, Felix Busque, Ramon Alibes, Mariona Sodupe, Salvador Ventura
Summary: This study discovered a series of novel halogenated kinetic stabilizers for transthyretin (TTR) through rational design and molecular dynamics (MD) simulations. Among them, M-23 displayed high affinity for TTR and demonstrated enhanced tetramer stability. The crystal structure confirmed the unprecedented protein-ligand contacts predicted by MD simulations.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Editorial Material
Cell Biology
Jaime Santos, Salvador Ventura, Irantzu Pallares
NEURAL REGENERATION RESEARCH
(2023)
Article
Multidisciplinary Sciences
Javier Garcia-Pardo, Andrea Bartolome-Nafria, Antonio Chaves-Sanjuan, Marcos Gil-Garcia, Cristina Visentin, Martino Bolognesi, Stefano Ricagno, Salvador Ventura
Summary: The study reports the cryo-electron microscopy structure of hnRNPDL-2 fibrils, revealing its stable, non-toxic, and nucleic acid-binding properties. The structure provides insights into the mechanism of hnRNPDL-2 fibrillation and its association with LGMD D3. Additionally, the study highlights how alternative splicing controls the assembly of different hnRNPDL isoforms, generating functional diversity.
NATURE COMMUNICATIONS
(2023)
Article
Plant Sciences
Carlos Pintado-Grima, Jaime Santos, Valentin Iglesias, Zoe Manglano-Artunedo, Irantzu Pallares, Salvador Ventura
Summary: Prion-like domains (PrLDs) are intrinsically disordered regions (IDRs) with low sequence complexity similar to yeast prion domains. Proteins containing PrLDs are involved in regulatory processes in different organisms. Within IDRs, regions with moderate amyloid propensity have the ability to autonomously assemble into amyloid fibrils. These regions, called cryptic amyloidogenic regions (CARs), are often rich in polar amino acids and evade detection from common bioinformatics screenings that focus on hydrophobic sequence stretches. CARs are evolutionarily conserved and have the potential to interact with other biomolecules. In this study, we identified and characterized CARs in prion-like proteins (pCARs) from plants, a group that has been less studied compared to other prionomes. We confirmed the amyloid potential of a selected pCAR from Arabidopsis thaliana and investigated functional enrichments and compositional bias of pCARs in plant prion-like proteins.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Nanoscience & Nanotechnology
Molood Behbahanipour, Roger Benoit, Susanna Navarro, Salvador Ventura
Summary: A novel nanoparticle has been developed that can neutralize SARS-CoV-2 virus. The nanoparticle is biocompatible and stable, and shows potential for therapeutic and diagnostic applications.
ACS APPLIED MATERIALS & INTERFACES
(2023)
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
Susanna Navarro, Marta Diaz-Caballero, Francesca Peccati, Lorena Roldan-Martin, Mariona Sodupe, Salvador Ventura
Summary: Enzymes fold into specific 3D protein structures and exhibit high catalytic efficiency and selectivity. Artificial amyloids have been shown to have catalytic activity and advantages over natural enzymes. A recent study found that short peptides can self-assemble into amyloid fibrils with catalytic activity by coordinating and retaining different divalent metal cations. These findings provide new insights into the design of artificial metalloenzymes and support the role of amyloid-like structures in the origin of life.
News Item
Biochemistry & Molecular Biology
Javier Garcia-Pardo, Salvador Ventura
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Aleksandra E. Badaczewska-Dawid, Aleksander Kuriata, Carlos Pintado-Grima, Javier Garcia-Pardo, Michal Burdukiewicz, Valentin Iglesias, Sebastian Kmiecik, Salvador Ventura
Summary: Protein aggregation is associated with aging and different pathologies, and is a challenge in the industrial production of biotherapeutics. Previous research in model organisms has provided insights into the biophysical principles of this process and led to the development of computational tools. A3D-MODB is a comprehensive database that allows for the study of protein aggregation in 12 model species and provides additional information for better understanding protein aggregation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Federica Nicolini, Toni Todorovski, Eduard Puig, Mireia Diaz-Lobo, Marta Vilaseca, Jesus Garcia, David Andreu, Ernest Giralt
Summary: Tumour suppressor p53 plays a crucial role in cancer development, but the tetramerisation mechanism of p53 is not fully understood. Mutations in p53, which occur in nearly 50% of cancers, can alter the oligomeric state of the protein and affect its biological function and cell fate decisions.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Medicinal
Francisca Pinheiro, Nathalia Varejao, Adria Sanchez-Morales, Filipa Bezerra, Susanna Navarro, Adrian Velazquez-Campoy, Felix Busque, Maria Rosario Almeida, Ramon Alibes, David Reverter, Irantzu Pallares, Salvador Ventura
Summary: The TTR chemical chaperone PITB has shown promising potential as a disease-modifying therapy for TTR amyloidosis. It selectively binds and stabilizes TTR in plasma, effectively inhibiting tetramer dissociation and aggregation. Pharmacokinetic studies in mice have confirmed optimal pharmacokinetic properties and lack of toxicity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
