Article
Biochemistry & Molecular Biology
Shogo Moriya, Michiko Hanazono, Takeshi Fukuhara, Katsuro Iwase, Nobutaka Hattori, Masaki Takiguchi
Summary: This study investigated the involvement of macrophages/microglia in the formation and spread of alpha-synuclein (αS) fibrils. Transgenic zebrafish expressing αS in macrophages/microglia showed accumulation of αS in neurons. Transcriptome analysis revealed changes in gene expression related to kinases, ubiquitin protein ligases, neuronal activity, and transport. Furthermore, αS fibrils formed from monomers in macrophages and were spread to neurons. The ubiquitin-proteasome system modulated αS fibrils. These findings suggest that macrophages play an essential role in the formation of αS aggregates and the pathogenesis of Parkinson's disease.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Nisha R. R. Dhanushkodi, Salema B. B. Abul Khair, Mustafa T. T. Ardah, M. Emdadul Haque
Summary: Mutations in ATP13A2 cause Kufor-Rakeb syndrome and affect the autophagic degradation of alpha-syn. Knocking down ATP13A2 in Drosophila results in increased levels of insoluble alpha-syn and decreased autophagic flux. ATP13A2 also affects dopaminergic neuron loss, sleep, and circadian activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Akua A. Karikari, Rhonda L. McFleder, Eliana Ribechini, Robert Blum, Valentin Bruttel, Susanne Knorr, Mona Gehmeyr, Jens Volkmann, Jonathan M. Brotchie, Fadhil Ahsan, Beatrice Haack, Camelia-Maria Monoranu, Ursula Keber, Rima Yeghiazaryan, Axel Pagenstecher, Tobias Heckel, Thorsten Bischler, Joerg Wischhusen, James B. Koprich, Manfred B. Lutz, Chi Wang Ip
Summary: The study confirms that alpha-synuclein-specific T cell responses can cause dopaminergic neurodegeneration and contribute to the pathogenesis of Parkinson's disease (PD) in a mouse model.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Biochemistry & Molecular Biology
Bingkuan Xu, Fengshuo Fan, Yunpeng Liu, Yinghui Liu, Lin Zhou, Haijia Yu
Summary: Lewy bodies and Lewy neurites are key pathological hallmarks of Parkinson's disease, with alpha-Synuclein (alpha-Syn) aggregation playing a crucial role. Mutations associated with familial PD affect alpha-Syn LLPS and its correlation with amyloid aggregation, but the exact mechanisms remain unclear.
Article
Biochemistry & Molecular Biology
Noemie Cresto, Camille Gardier, Marie-Claude Gaillard, Francesco Gubinelli, Pauline Roost, Daniela Molina, Charlene Josephine, Noelle Dufour, Gwenaelle Auregan, Martine Guillermier, Sueva Bernier, Caroline Jan, Pauline Gipchtein, Philippe Hantraye, Marie-Christine Chartier-Harlin, Gilles Bonvento, Nadja Van Camp, Jean-Marc Taymans, Karine Cambon, Geraldine Liot, Alexis-Pierre Bemelmans, Emmanuel Brouillet
Summary: The C-terminal domain of mutated LRRK2 was shown to induce neurodegeneration of dopaminergic neurons independently of its N-terminal domains and through cell-autonomous mechanisms. Mutated alpha-syn toxicity can be enhanced by the C-terminal domain of LRRK2 through cell-autonomous mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Behavioral Sciences
Thomas Musacchio, Jing Yin, Fabian Kremer, James B. Koprich, Jonathan M. Brotchie, Jens Volkmann, Chi Wang Ip
Summary: Degeneration of the nigrostriatal tract is a characteristic of Parkinson's disease (PD). This study found that nuclear factor Nrf2 and histone deacetylase 1 (HDAC1) play an important role in regulating the degeneration of neurons. The impairment of axons is associated with motor deficits, but does not directly reflect neurodegeneration.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Article
Neurosciences
Lisa Rauschenberger, Jennifer Behnke, Alexander Grotemeyer, Susanne Knorr, Jens Volkmann, Chi Wang Ip
Summary: The pathogenesis of Parkinson's disease is closely related to aging, and inflammation is also an additional factor in disease development. In a mouse model of Parkinson's disease, age and inflammation are found to be associated with dopaminergic neurodegeneration, and the response of T cells and glial cells is involved in the process of neurodegeneration.
NEUROBIOLOGY OF DISEASE
(2022)
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
Chemistry, Multidisciplinary
Xiuxiu Yang, Xiaofang Zhao, Hansen Zhao, Fengwei Liu, Sichun Zhang, Claire Xi Zhang, Zhongqiang Yang
Summary: The phospholipid-decorated liquid crystal-aqueous interface is constructed to investigate the binding between alpha-synucleins and phospholipid. Deep learning analysis can accurately identify single point mutant alpha-synucleins.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Ruben Pavia-Collado, Valentin Coppola-Segovia, Lluis Miquel-Rio, Diana Alarcon-Aris, Raquel Rodriguez-Aller, Maria Torres-Lopez, Veronica Paz, Esther Ruiz-Bronchal, Leticia Campa, Francesc Artigas, Andres Montefeltro, Raquel Revilla, Analia Bortolozzi
Summary: Experimental studies have shown that using indatraline-conjugated antisense oligonucleotide can effectively reduce the synthesis of alpha-synuclein in specific neurons of mice and nonhuman primates, potentially providing a new therapeutic strategy for Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Rommani Mondal, Anthony-David Tawatao Campoy, Christopher Liang, Jogeshwar Mukherjee
Summary: The M83 transgenic mouse line is a model of alpha-synucleinopathy found in Parkinson's disease, useful for studying non-motor deficits in the early stages of PD. Research findings indicate metabolic changes and neurodegenerative symptoms in this PD mouse model, leading to progressive motor dysfunction and death. 9-month-old male and female Hualpha-Syn (A53) mice exhibit up to 30% decrease in [F-18]FDG uptake, consistent with cortical hypometabolism observed in PD patients.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Neurosciences
Aishwarya Raj, Alka Kaushal, Indrani Datta
Summary: The exposure to extracellular alpha-synuclein leads to dysfunction in astrocytes regarding antioxidant mechanisms and glutamate metabolism, with a more severe impact observed in aggregated and mutated forms of the peptide.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Multidisciplinary Sciences
Houfang Long, Weitong Zheng, Yang Liu, Yunpeng Sun, Kun Zhao, Zhenying Liu, Wencheng Xia, Shiran Lv, Zhengtao Liu, Dan Li, Kai-Wen He, Cong Liu
Summary: Our research has shown that WT mice inoculated with the human E46K mutant alpha-syn fibril (hE46K) strain exhibit early-onset motor deficits and morphologically different alpha-syn aggregation compared to those inoculated with the human WT fibril (hWT) strain. Cryoelectron microscopy has revealed that the hE46K strain induces both human and mouse WT alpha-syn monomers to form the fibril structure of the hE46K strain at the near-atomic level. Furthermore, the induced hWT strain inherits most of the pathological traits of the hE46K strain, suggesting that mutant strains' structural and pathological features could be propagated by the WT alpha-syn and amplified in familial Parkinson's diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Geriatrics & Gerontology
Meige Zheng, Yanchang Liu, Zhaoming Xiao, Luyan Jiao, Xian Lin
Summary: Loss of PV+ neurons was observed in patients with end-stage PD and an old-aged PD model. The accumulation of α-synuclein in the SNR was accompanied by the degeneration of PV+ neurons and the generation of apoptotic neurons. PV+ neurons might undergo a transitional stage from decreased PV expression to increased NeuN expression and then to TUNEL expression. NeuN may serve as an indicator for the degeneration of SNR PV+ neurons.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Clinical Neurology
Kensuke Daida, Shotaro Shimonaka, Kahori Shiba-Fukushima, Jun Ogata, Hiroyo Yoshino, Ayami Okuzumi, Taku Hatano, Yumiko Motoi, Tomoki Hirunagi, Masahisa Katsuno, Hideo Shindou, Manabu Funayama, Kenya Nishioka, Nobutaka Hattori, Yuzuru Imai
Summary: The V15A variant of α-Synuclein (α-Syn) may be associated with the development of Parkinson's disease (PD). This variant has reduced affinity for phospholipids and increased propagation activity compared to the wild-type.
MOVEMENT DISORDERS
(2022)
Correction
Biochemistry & Molecular Biology
Damiano Piovesan, Francesco Tabaro, Ivan Micetic, Marco Necci, Federica Quaglia, Christopher J. Oldfield, Maria Cristina Aspromonte, Norman E. Davey, Radoslav Davidovic, Zsuzsanna Dosztanyi, Arne Elofsson, Alessandra Gasparini, Andras Hatos, Andrey V. Kajava, Lajos Kalmar, Emanuela Leonardi, Tamas Lazar, Sandra Macedo-Ribeiro, Mauricio Macossay-Castillo, Attila Meszaros, Giovanni Minervini, Nikoletta Murvai, Jordi Pujols, Daniel B. Roche, Edoardo Salladini, Eva Schad, Antoine Schramm, Beata Szabo, Agnes Tantos, Fiorella Tonello, Konstantinos D. Tsirigos, Nevena Veljkovic, Salvador Ventura, Wim Vranken, Per Warholm, Vladimir N. Uversky, A. Keith Dunker, Sonia Longhi, Peter Tompa, Silvio C. E. Tosatto
NUCLEIC ACIDS RESEARCH
(2017)
Article
Biochemistry & Molecular Biology
Damiano Piovesan, Francesco Tabaro, Ivan Micetic, Marco Necci, Federica Quaglia, Christopher J. Oldfield, Maria Cristina Aspromonte, Norman E. Davey, Radoslav Davidovic, Zsuzsanna Dosztanyi, Arne Elofsson, Alessandra Gasparini, Andras Hatos, Andrey V. Kajava, Lajos Kalmar, Emanuela Leonardi, Tamas Lazar, Sandra Macedo-Ribeiro, Mauricio Macossay-Castillo, Attila Meszaros, Giovanni Minervini, Nikoletta Murvai, Jordi Pujols, Daniel B. Roche, Edoardo Salladini, Eva Schad, Antoine Schramm, Beata Szabo, Agnes Tantos, Fiorella Tonello, Konstantinos D. Tsirigos, Nevena Veljkovic, Salvador Ventura, Wim Vranken, Per Warholm, Vladimir N. Uversky, A. Keith Dunker, Sonia Longhi, Peter Tompa, Silvio C. E. Tosatto
NUCLEIC ACIDS RESEARCH
(2017)
Article
Multidisciplinary Sciences
Nai-Chieh Liu, Eileen L. Troconis, Lajos Kalmar, David J. Price, Hattie E. Wright, Vicki J. Adams, David R. Sargan, Jane F. Ladlow
Article
Veterinary Sciences
Nai-Chieh Liu, Gerhard U. Oechtering, Vicki J. Adams, Lajos Kalmar, David R. Sargan, Jane F. Ladlow
VETERINARY SURGERY
(2017)
Article
Veterinary Sciences
Nai-Chieh Liu, Eileen L. Troconis, Matthew McMillan, Marie-Aude Genain, Lajos Kalmar, David J. Price, David R. Sargan, Jane F. Ladlow
VETERINARY RADIOLOGY & ULTRASOUND
(2018)
Editorial Material
Veterinary Sciences
Jane Ladlow, Nai-Chieh Liu, Lajos Kalmar, David Sargan
Article
Veterinary Sciences
Nai-Chieh Liu, Marie-Aude Genain, Lajos Kalmar, David R. Sargan, Jane F. Ladlow
VETERINARY SURGERY
(2019)
Article
Infectious Diseases
Xiaoliang Ba, Lajos Kalmar, Nazreen F. Hadjirin, Heidrun Kerschner, Petra Apfalter, Fiona J. Morgan, Gavin K. Paterson, Samantha L. Girvan, Rui Zhou, Ewan M. Harrison, Mark A. Holmes
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2019)
Article
Biochemistry & Molecular Biology
Beata Szabo, Tamas Horvath, Eva Schad, Nikoletta Murvai, Agnes Tantos, Lajos Kalmar, Lucia Beatriz Chemes, Kyou-Hoon Han, Peter Tompa
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Behavioral Sciences
Daniel Baksa, Xenia Gonda, Nora Eszlari, Peter Petschner, Veronika Acs, Lajos Kalmar, J. F. William Deakin, Gyorgy Bagdy, Gabriella Juhasz
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2020)
Article
Genetics & Heredity
Christopher A. Jenkins, Lajos Kalmar, Kaspar Matiasek, Lorenzo Mari, Kaisa Kyostila, Hannes Lohi, Ellen C. Schofield, Cathryn S. Mellersh, Luisa De Risio, Sally L. Ricketts
Article
Biochemistry & Molecular Biology
Monika Bokor, Agnes Tantos, Peter Tompa, Kyou-Hoon Han, Kalman Tompa
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Monika Bokor, Agnes Tantos
Summary: The study found that A53T alpha-synuclein aggregates have more extensive beta sheet contents, and the energies of intermolecular interactions and secondary structures formed during polymerization fall within a specific range. Amyloids lose more hydration water compared to oligomers, and new intermolecular bonds are formed during aggregation.
Article
Genetics & Heredity
Lajos Kalmar, Srishti Gupta, Iain R. L. Kean, Xiaoliang Ba, Nazreen Hadjirin, Elizabeth M. Lay, Stefan P. W. de Vries, Michael Bateman, Harriet Bartlet, Juan Hernandez-Garcia, Alexander W. Tucker, Olivier Restif, Mark P. Stevens, James L. N. Wood, Duncan J. Maskell, Andrew J. Grant, Mark A. Holmes
Summary: Shotgun metagenomics is a powerful tool for identifying AMR genes in microbiomes but lacks the ability to link extrachromosomal DNA to bacterial chromosomes. We present HAM-ART, a comprehensive pipeline for generating metagenome-assembled genomes that includes both chromosomal and extrachromosomal AMR genes. The pipeline's performance was demonstrated in a study comparing pig faecal microbiomes from low- and high-antimicrobial use farms, revealing significant differences in AMR gene distribution.
Article
Chemistry, Physical
Kalman Tompa, Monika Bokor, Dorina Agner, David Ivan, Denes Kovacs, Tamas Verebelyi, Peter Tompa