Review
Biochemistry & Molecular Biology
A. Anandhan, W. Chen, N. Nguyen, L. Madhavan, M. Dodson, D. D. Zhang
Summary: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the accumulation of alpha-synuclein and its negative effects on neuronal function and viability. This study demonstrates that loss of NRF2, a critical anti-ferroptotic mediator, increases markers of ferroptosis in PD-relevant brain regions. The increased ferroptosis is associated with age and genotype-dependent increase in alpha-syn pathology and behavioral deficits. The findings suggest targeting the vicious cycle of alpha-syn overexpression and NRF2 suppression as a potential means of preventing PD onset and progression.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Neurosciences
Danyu Lin, Yao Li, Kaixun Huang, Ying Chen, Xiuna Jing, Yanran Liang, Lulu Bu, Sudan Peng, Shaowei Zeng, Tetsuya Asakawa, Enxiang Tao
Summary: In this study, we found that T199678 regulates the expression of KLF9 in alpha-syn exposed cells, while KLF9 does not affect the expression of T199678. miR-519-3p may play a contributing role in this regulation. Furthermore, upregulation of T199678 can downregulate ROS levels induced by alpha-syn, indicating its anti-oxidative role in alpha-syn-related mechanisms.
BRAIN RESEARCH BULLETIN
(2022)
Article
Medicine, Research & Experimental
Tatsuya Karaki, Hisao Haniu, Yoshikazu Matsuda, Tamotsu Tsukahara
Summary: This study demonstrates the inhibitory effect of a certain lysophospholipids (LPLs) species extracted from porcine liver decomposition product (PLDP) on alpha-Synuclein (alpha-Syn) aggregation. Lysophosphatidylcholine (LPC) 16:0, LPC18:0, LPC18:1, and lysophosphatidylethanolamine (LPE) 16:0 contained in PLDP-extracted lipids (PEL) were found to strongly inhibit alpha-Syn aggregation. These findings suggest the potential of PLDP-derived LPLs as effective therapeutic agents against alpha-Synucleinopathies.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Kristina Fredriksen, Stefanos Aivazidis, Karan Sharma, Kevin J. Burbidge, Caleb Pitcairn, Friederike Zunke, Eilrayna Gelyana, Joseph R. Mazzulli
Summary: GBA1 mutations that encode lysosomal beta-glucocerebrosidase (GCase) cause Gaucher disease and are risk factors for synucleinopathies. The study found that alpha-synuclein neuropathology induced by GCase depletion depends on neuronal maturity, alpha-synuclein physiology, and specific accumulation of long-chain glycosphingolipid substrates. Reduction of long-chain glycosphingolipids can ameliorate alpha-synuclein pathology.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
S. Jadavi, S. Dante, L. Civiero, M. Sandre, L. Bubacco, L. Tosatto, P. Bianchini, C. Canale, A. Diaspro
Summary: In a previous study, it was shown that the coexistence of different aggregation pathways of insulin and A beta peptides was due to suboptimal proteins labeling strategies. However, this phenomenon could not be considered valid for all molecular systems. In this study, the aggregation process of alpha-syn was investigated, and it was found that a specific labeling method could avoid labeling artifacts. These results highlight the importance of careful designing the labeling strategy for the molecular system under investigation.
Article
Biochemistry & Molecular Biology
Jianmin Si, Chris van den Haute, Evy Lobbestael, Shaun Martin, Sarah van Veen, Peter Vangheluwe, Veerle Baekelandt
Summary: ATP13A2 loss impairs lysosomal membrane integrity and induces alpha-synuclein multimerization, while overexpression has a protective effect on alpha-synuclein by promoting ubiquitin-proteasome system activity and reducing alpha syn membrane association. Additionally, ATP13A2 promotes the secretion of alpha-synuclein through nanovesicles, suggesting a regulatory function independent of ATPase and transport activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Letter
Clinical Neurology
Aravind Ganesh, Steven Galetta
Summary: The study found lower total alpha-synuclein levels in the CSF of PD patients with high sensitivity but low specificity compared to HCs. Alpha-synuclein immunoreactivity in skin and submandibular gland was specific for PD but not sensitive. There are ongoing debates and uncertainties in methodology surrounding the detection of synuclein in tissue samples.
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)
Article
Biochemistry & Molecular Biology
Zohra Rahmani, Satya Surabhi, Francisca Rojo-Cortes, Amina Dulac, Andreas Jenny, Serge Birman
Summary: The lack of Lamp1 in fruit flies increases susceptibility to oxidative stress and neurotoxicity caused by alpha-synuclein, suggesting a protective role of Lamp1 in Parkinson's disease models. Lamp1 promotes the formation of non-pathogenic aggregates, neutralizing the toxicity of alpha-synuclein.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Emilio Fernandez-Espejo, Fernando Rodriguez de Fonseca, Juan Suarez, Eduardo Tolosa, Dolores Vilas, Iban Aldecoa, Joan Berenguer, Fatima Damas-Hermoso
Summary: This study found that the concentrations of native alpha-synuclein and nitrated proteins in the saliva of patients with idiopathic Parkinson's disease (IPD) are similar to those in the control group, with no correlation with clinical features. Additionally, Lewy-type inclusions expressing 3-nitrotyrosine-alpha-synuclein were observed in the submandibular glands of IPD patients but not controls, suggesting this could be a useful diagnostic technique for IPD.
Article
Cell Biology
Alice Prieto Huarcaya, Susy Drobny, Andre R. A. Marques, Alessandro Di Spiezio, Jan Philipp Dobert, Denise Balta, Christian Werner, Tania Rizo, Lisa Gallwitz, Simon Bub, Iva Stojkovska, Nandkishore R. Belur, Jens Fogh, Joseph R. Mazzulli, Wei Xiang, Amitkumar Fulzele, Mario Dejung, Markus Sauer, Beate Winner, Stefan Rose-John, Philipp Arnold, Paul Saftig, Friederike Zunke
Summary: This study suggests that enhancing SNCA degradation through the application of rHsCTSD can reduce SNCA aggregates in the brains of PD patients and restore endo-lysosome and autophagy function.
Article
Biology
Jessica Tittelmeier, Silke Druffel-Augustin, Ania Alik, Ronald Melki, Carmen Nussbaum-Krammer
Summary: Synucleinopathies are neurodegenerative diseases caused by the accumulation of pathological alpha-synuclein. The study used FLIM to investigate the aggregation of alpha-synuclein and found that different conformational polymorphs of alpha-synuclein exhibit distinct fluorescence lifetimes. Moreover, these polymorphs are processed differently by cellular clearance pathways, resulting in fibrillar species with increased seeding capacity.
COMMUNICATIONS BIOLOGY
(2022)
Article
Neurosciences
Alberto Delaidelli, Mette Richner, Lixiang Jiang, Amelia van der Laan, Ida Bergholdt Jul Christiansen, Nelson Ferreira, Jens R. Nyengaard, Christian B. Vaegter, Poul H. Jensen, Ian R. Mackenzie, Poul H. Sorensen, Asad Jan
Summary: The pathological accumulation of alpha-synuclein impairs redox homeostasis in the nervous system, leading to nuclear NRF2 accumulation and alterations in NRF2-responsive genes. Using a transgenic mouse model, it was observed that neuronal populations with phosphorylated aSyn showed increased nuclear NRF2 and abnormal anti-oxidant and inflammatory gene response in the affected neuraxis. Boosting neuronal anti-oxidant response may be a promising strategy to mitigate neurodegeneration in PD and related diseases.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Vinod Kumar Meena, Vijay Kumar, Shivani Karalia
Summary: The natural extract of Ocimum sanctum (OS) has been found to inhibit the aggregation of alpha-Synuclein (alpha-Syn), suggesting a potential therapeutic intervention against Parkinson's disease (PD) and other aggregation-related disorders. The study demonstrates the inhibitory and disaggregation effects of OS extract on alpha-Synuclein, as well as its protective effect on neuroblastoma cells against fibril-induced cytotoxicity. Docking studies also indicate the binding of OS extract with alpha-Synuclein, paving the way for further research on potential therapeutic strategies.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
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
Biochemical Research Methods
Yonghui Dong, Yana Kazachkova, Meng Gou, Liat Morgan, Tal Wachsman, Ehud Gazit, Rune Isak Dupont Birkler
Summary: RawHummus is an R Shiny app for automated raw data quality control in metabolomics studies. It generates comprehensive QC reports with interactive plots and tables, summary statistics, and detailed explanations.
Article
Chemistry, Multidisciplinary
Yu Chen, Sarah Guerin, Hui Yuan, Joseph O'Donnell, Bin Xue, Pierre-Andre Cazade, Ehtsham Ul Haq, Linda J. W. Shimon, Sigal Rencus-Lazar, Syed A. M. Tofail, Yi Cao, Damien Thompson, Rusen Yang, Ehud Gazit
Summary: The understanding of the piezoelectricity in biological materials is still incomplete at the molecular level, which hinders the rational design of eco-friendly piezoelectric supramolecular materials. This study demonstrates a new type of adaptive piezoelectric supramolecular material by observing the mechanoresponses of Piezo channel proteins and amplifying the electromechanical response of a peptide metal-organic framework through guest-host interactions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Liat Morgan, Rune Isak Dupont Birkler, Shira Shaham-Niv, Yonghui Dong, Tal Wachsman, Lior Carmi, Boris Yakobson, Lihi Adler-Abramovich, Hagit Cohen, Joseph Zohar, Melissa Bateson, Ehud Gazit
Summary: This study investigated the acute systemic impact of major psychological stress on the body using a pig model. The results showed that major psychological stress led to decreases in several important molecular levels, which may be implicated in the pathology of human psychological disorders and neurodegenerative disease. The study provides important insights into the acute effects of psychological stress on the metabolome and suggests potential biomarkers for stress-related disorders.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Yan Zhang, Qi Li, Haoran Wu, Yancheng Wang, Yan Wang, Sigal Rencus-Lazar, Yurong Zhao, Jiqian Wang, Deqing Mei, Hai Xu, Ehud Gazit, Kai Tao
Summary: Amino acids are bio-building blocks that play various roles in metabolic activities. Supramolecular structures formed by amino acids exhibit amyloid-like characteristics, which are driven by hydrogen bonds and play critical roles in the properties and applications of amino acid assemblies. Tyrosine-based superstructures have diverse properties and functions, making them promising next-generation biomaterials for biomedical applications. However, modulating the energetically stable supramolecular structures of tyrosine-based organizations is challenging. By assembling L-Y and D-Y, the secondary structures of the supramolecular assemblies can be modulated, leading to distinct organization kinetics and modulation of physicochemical properties.
Review
Chemistry, Multidisciplinary
Nikhil Bajpayee, Thangavel Vijayakanth, Sigal Rencus-Lazar, Sneha Dasgupta, Aamod V. Desai, Rahul Jain, Ehud Gazit, Rajkumar Misra
Summary: Flexible and biocompatible metal peptide frameworks (MPFs) have been developed from short and ultra-short peptides for various applications such as greenhouse gas storage, molecular recognition, and chiral transformations. Recently, specifically folded peptides have been utilized to fabricate metal helix frameworks (MHFs) that control the formation of three-dimensional (3D)-MHFs. This article describes the recent progress of metal-driven folded peptide assembly for constructing 3D porous structures with potential applications in energy storage, chiral recognition, and biomedical fields, serving as an alternative to conventional metal-organic frameworks (MOFs).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Geriatrics & Gerontology
Rony M. Sayig-Keren, Moria Dagan, Pablo Cornejo Thumm, Marina Brozgol, Eran Gazit, Brad Manor, Jeffrey M. Hausdorff
Summary: This study examines the effects of theta-tACS on dual-task walking and cognitive function in older adults. The results show that theta-tACS and tDCS have similar effects in reducing dual-task costs, suggesting that theta-tACS may influence the fronto-parietal network and improve dual-tasking.
Review
Chemistry, Multidisciplinary
Vijay Bhooshan Kumar, Ifat Sher, Sigal Rencus-Lazar, Ygal Rotenstreich, Ehud Gazit
Summary: Carbon quantum dots (CDs) are emerging carbonaceous nanomaterials with excellent fluorescent properties, small size, cell and tissue penetration ability, ease of synthesis, surface modification, low cytotoxicity, and superior water dispersion. They have great potential as bioimaging probes, drug carriers, and disease diagnostics. Functionalized CDs show promise in the diagnosis and treatment of ocular diseases, including macular and anterior segment diseases, as well as targeting A beta amyloids in the retina.
Article
Multidisciplinary Sciences
Luca Palmerini, Luca Reggi, Tecla Bonci, Silvia Del Din, M. Encarna Mico-Amigo, Francesca Salis, Stefano Bertuletti, Marco Caruso, Andrea Cereatti, Eran Gazit, Anisoara Paraschiv-Ionescu, Abolfazl Soltani, Felix Kluge, Arne Kuederle, Martin Ullrich, Cameron Kirk, Hugo Hiden, Ilaria D'Ascanio, Clint Hansen, Lynn Rochester, Claudia Mazza, Lorenzo Chiari
Summary: This study provides an example of organizing, integrating, and storing movement data recorded from different wearables and gold standard technologies. The guidelines derived from the experience of a large multi-centric study offer support for accessing, understanding, and reusing available data, promoting standardization and integration in other studies, and facilitating comparison of recorded data in the scientific community.
Review
Pharmacology & Pharmacy
Vijay Bhooshan Kumar, Om Shanker Tiwari, Gal Finkelstein-Zuta, Sigal Rencus-Lazar, Ehud Gazit
Summary: Tissue engineering is focused on restoring or replacing damaged tissues, and peptide self-assembly, particularly RGD peptides, is an effective method for developing tissue structures and functionalities. This review summarizes the progress of RGD application in tissue and organ development, examines its impact on TE efficacy in clinical and preclinical studies, and outlines recent advancements in the use of RGD functionalized biomaterials for tissue regeneration.
Article
Chemistry, Multidisciplinary
Ruth Aizen, Zohar A. Arnon, Or Berger, Antonella Ruggiero, Dor Zaguri, Noam Brown, Evgeny Shirshin, Inna Slutsky, Ehud Gazit
Summary: Nucleobase crystals have unique fluorescence properties in the visible spectrum, unlike their monomeric counterparts. Additionally, some nucleobases exhibit a red edge excitation shift, which is uncommon in the field of organic supramolecular materials and may have implications in therapeutic and materials science.
NANOSCALE ADVANCES
(2023)
Article
Chemistry, Multidisciplinary
Om Shanker Tiwari, Ruth Aizen, Massimiliano Meli, Giorgio Colombo, Linda J. W. Shimon, Noam Tal, Ehud Gazit
Summary: Molecular self- and co-assembly have the ability to form diverse and well-defined supramolecular structures with notable physical properties. By exploring the co-assembly of L-His with different aromatic amino acids, including Phe, Tyr, and Trp, we expanded the structural space of amino acid nanomaterials. The best seamless co-assembly was observed between L-His and L-Phe, resulting in the formation of single crystals.
Article
Chemistry, Physical
Yunxiao Wang, Qiang Geng, Yan Zhang, Lihi Adler-Abramovich, Xinyuan Fan, Deqing Mei, Ehud Gazit, Kai Tao
Summary: In this article, the mechanisms underlying the self-assembly of 9-fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF), the preparation methodologies of Fmoc-FF hydrogels, and the properties and applications of Fmoc-FF self-assemblies are systematically summarized. The contemporary shortcomings that limit the development of Fmoc-FF self-assembly are raised, and alternative solutions and future research perspectives are proposed.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2023)
Article
Chemistry, Physical
Vijay Bhooshan Kumar, Busra Ozguney, Anastasia Vlachou, Yu Chen, Ehud Gazit, Phanourios Tamamis
Summary: The design of novel cancer drug nanocarriers is crucial in cancer therapeutics. Nanomaterials, especially self-assembling peptides, show great potential in drug delivery by promoting drug release and stability while reducing side effects. This review highlights the importance of metal coordination, structure stabilization, cyclization, and minimalism in the design of peptide self-assembled nanocarriers for cancer drug delivery. Future perspectives suggest that incorporating these materials into single or multicomponent systems could lead to novel classes of cancer drug delivery systems.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Computer Science, Interdisciplinary Applications
Gaelle Prigent, Kamiar Aminian, Andrea Cereatti, Francesca Salis, Tecla Bonci, Kirsty Scott, Claudia Mazza, Lisa Alcock, Silvia Del Din, Eran Gazit, Clint Hansen, Anisoara Paraschiv-Ionescu
Summary: This study aims to validate a robust walking detection algorithm using a single foot-worn inertial measurement unit (IMU) in real-life settings. Accurate walking detection was obtained, with sensitivity and specificity of 98% and 91% respectively. A validated algorithm would pave the way for assessing patient performance and gait quality in real-world conditions.
MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING
(2023)
Article
Biotechnology & Applied Microbiology
Francesca Salis, Stefano Bertuletti, Tecla Bonci, Marco Caruso, Kirsty Scott, Lisa Alcock, Ellen Buckley, Eran Gazit, Clint Hansen, Lars Schwickert, Kamiar Aminian, Clemens Becker, Philip Brown, Anne-Elie Carsin, Brian Caulfield, Lorenzo Chiari, Ilaria D'Ascanio, Silvia Del Din, Bjoern M. Eskofier, Judith Garcia-Aymerich, Jeffrey M. Hausdorff, Emily C. Hume, Cameron Kirk, Felix Kluge, Sarah Koch, Arne Kuederle, Walter Maetzler, Encarna M. Mico-Amigo, Arne Mueller, Isabel Neatrour, Anisoara Paraschiv-Ionescu, Luca Palmerini, Alison J. Yarnall, Lynn Rochester, Basil Sharrack, David Singleton, Beatrix Vereijken, Ioannis Vogiatzis, Ugo Della Croce, Claudia Mazza, Andrea Cereatti
Summary: This study presents a wearable multi-sensor system (INDIP) that accurately assesses people's gait in real-world conditions. The system performed well in different cohorts and gait patterns, and was easy to use. Therefore, it can be considered a valid and feasible solution for analyzing gait in real-world conditions.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
