Article
Biochemistry & Molecular Biology
Caterina Nardella, Francesca Malagrino, Livia Pagano, Serena Rinaldo, Stefano Gianni, Angelo Toto
Summary: SH2 domains are protein-protein interaction modules that recognize and bind phosphorylated tyrosine sequences. SHP2, a protein phosphatase, interacts with various partners through its SH2 domains, such as N-SH2 and C-SH2. The interaction between SH2 domains and ligands involves electrostatic interactions, with a conserved histidine residue playing a key role.
Article
Neurosciences
Julie van der Zee, Lubina Dillen, Yalda Baradaran-Heravi, Helena Gossye, Cemile Kocoglu, Ivy Cuyt, Bart Dermaut, Anne Sieben, Jonathan Baets, Peter De Jonghe, Rik Vandenberghe, Peter De Deyn, Patrick Cras, Sebastiaan Engelborghs, Christine Van Broeckhoven
Summary: The RBP gene RBM45 is genetically implicated in the FTD-ALS spectrum, with mutations leading to cytoplasmic redistribution and co-aggregation with other RBPs, potentially causing persistent toxic inclusion formation.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Geriatrics & Gerontology
Di He, Yan, Xu, Mingsheng Liu, Liying Cui
Summary: Amyotrophic lateral sclerosis (ALS) is a genetically complex neurodegenerative disease that is associated with immune dysfunction. Neuroinflammation, characterized by abnormal immune cell activation and excessive production of inflammatory cytokines, plays a significant role in the pathophysiology of ALS. This review examines recent evidence on the role of ALS-associated mutant genes in immune dysregulation, with a focus on the cGAS-STING signaling pathway and m6A-mediated immune regulation in neurodegeneration. It also discusses immune cell perturbation in both the central nervous system and peripheral tissues in ALS, as well as advancements in genetic and cell-based therapies for ALS. Understanding the complex relationship between ALS and neuroinflammation is crucial for the development of effective treatments for this debilitating disorder.
Article
Clinical Neurology
Jonathan D. Glass, Ramita Dewan, Jinhui Ding, J. Raphael Gibbs, Clifton Dalgard, Pamela J. Keagle, Shankaracharya, Alberto Garcia-Redondo, Bryan J. Traynor, Ruth Chia, John E. Landers
Summary: Intermediate CAG (polyQ) expansions in the ATXN2 gene are associated with amyotrophic lateral sclerosis (ALS). Expansions of >= 31 repeats increase the risk for ALS and even greater risk for ALS with frontotemporal dementia (FTD).
Review
Biochemistry & Molecular Biology
Allison A. Dilliott, Catherine M. Andary, Meaghan Stoltz, Andrey A. Petropavlovskiy, Sali M. K. Farhan, Martin L. Duennwald
Summary: Protein misfolding is a common basis for neurodegenerative diseases like ALS. Cellular protein quality control can prevent misfolding, but stressors like reactive oxygen species, genetic mutations, and aging can lead to misfolding. DnaJC7, a molecular chaperone, can prevent misfolding and deal with misfolded proteins through degradation systems or autophagy. Pathogenic variants in the DnaJC7 gene contribute to ALS, but the underlying molecular pathophysiology and function of DnaJC7 remain largely unknown.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Yara Al Ojaimi, Audrey Dangoumau, Hugo Alarcan, Rudolf Hergesheimer, Patrick Vourc'h, Philippe Corcia, Debora Lanznaster, Helene Blasco
Summary: ALS is a fatal neurodegenerative disease without effective treatment. TDP-43, a major therapeutic target in ALS, has been studied for its cellular functions and pathological effects. Various pathways have been explored for mitigating TDP-43 pathology in ALS.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Clinical Neurology
C. Appleby-Mallinder, E. Schaber, J. Kirby, P. J. Shaw, J. Cooper-Knock, P. R. Heath, J. R. Highley
Summary: The study revealed higher levels of 5mC and 5hmC in lower motor neurones (LMNs) of the spinal cord in ALS patients. LMNs with TDP43 pathology showed lower levels of nuclear 5mC and 5hmC, suggesting a particular impact on RNA metabolism.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Review
Clinical Neurology
Michael Benatar, Joanne Wuu, Caroline McHutchison, Ronald B. Postuma, Bradley F. Boeve, Ronald Petersen, Christopher A. Ross, Howard Rosen, Jalayne J. Arias, Stephanie Fradette, Michael P. McDermott, Jeremy Shefner, Christine Stanislaw, Sharon Abrahams, Stephanie Cosentino, Peter M. Andersen, Richard S. Finkel, Volkan Granit, Anne-Laure Grignon, Jonathan D. Rohrer, Corey T. McMillan, Murray Grossman, Ammar Al-Chalabi, Martin R. Turner
Summary: Significant progress has been made in understanding the pre-symptomatic phase of amyotrophic lateral sclerosis. Advances in other neurodegenerative diseases provide valuable insights and highlight opportunities for discovery in ALS. Biomarkers play a critical role in studying pre-symptomatic ALS and are essential for early therapeutic intervention and disease prevention.
Review
Biochemistry & Molecular Biology
Teresa Pardo-Moreno, Himan Mohamed-Mohamed, Sami Suleiman-Martos, Juan Jose Ramos-Rodriguez, Antonio Rivas-Dominguez, Lucia Melguizo-Rodriguez, Jose L. Gomez-Urquiza, Beatriz Bermudez-Pulgarin, Victoria Garcia-Morales
Summary: The aim of this study was to analyze the possible relationship between the rate of disease progression and plasma lipid levels at the early stage of ALS. The results of the meta-analytic study suggest that there is no clear relationship between the symptoms observed in ALS patients and the plasma lipid levels. Further research expansion and geographic diversity would be of interest.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Carlota Jauregui, Idoia Blanco-Luquin, Monica Macias, Miren Roldan, Cristina Caballero, Inma Pagola, Maite Mendioroz, Ivonne Jerico
Summary: This study investigates the expression patterns of microglial-related genes in ALS spinal cord, and suggests the presence of a DAM-mediated inflammatory response and the significant role of TREM2 in the immune function of microglia in ALS.
Review
Neurosciences
Jeremy S. Lum, Justin J. Yerbury
Summary: Protein homeostasis plays a crucial role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Pathological accumulation of ALS-associated proteins occurs within the axo-synaptic compartment of motor neurons, leading to synaptic dysfunction. The earliest pathological alterations in ALS occur at the synapse, prior to motor neuron loss.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Genetics & Heredity
Jiahao Cai, Xiong Chen, Hongxuan Wang, Zixin Wei, Mei Li, Xiaoming Rong, Xiangpen Li, Ying Peng
Summary: The study found no causal relationship between iron status and the risk of ALS. Efforts to change iron status to reduce ALS incidence may be impractical.
FRONTIERS IN GENETICS
(2021)
Article
Neurosciences
Mandana Hunter, Krista J. Spiller, Myrna A. Dominique, Hong Xu, Francis W. Hunter, Terry C. Fang, Rebecca G. Canter, Christopher J. Roberts, Richard M. Ransohoff, John Q. Trojanowski, Virginia M-Y Lee
Summary: The microglial reaction in TDP-43 proteinopathy during ALS progression involves differential gene expression profiles in spinal cord and cortex microglia. Specific genes associated with chemotaxis, phagocytosis, inflammation, and production of neuroprotective factors are upregulated during disease progression and recovery, providing insights into functional recovery after neuronal insult.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Bradley Roberts, Frances Theunissen, Francis L. Mastaglia, P. Anthony Akkari, Loren L. Flynn
Summary: This review provides a comprehensive overview of the literature on the etiology and development of ALS, as well as its commonalities with synucleinopathy disorders. It discusses the involvement of alpha Syn in ALS and motor neuron disease pathology, along with current theories and strategies for therapeutics in ALS treatment, with a focus on small molecule RNA technologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Wenzhi Chen, Ling Guo, Manna Li, Caihui Wei, Shu Li, Renshi Xu
Summary: This review explores the roles of mitochondrial dysfunction, protein quality control, and epigenetic mechanisms in the pathogenesis of ALS. It emphasizes the need for further research to fully understand the mechanisms underlying ALS.
Article
Biochemistry & Molecular Biology
Edoardo Del Poggetto, Francesco Bemporad, Francesca Tatini, Fabrizio Chiti
ACS CHEMICAL BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Predrag Kukic, Hoi Tik Alvin Leung, Francesco Bemporad, Francesco A. Aprile, Janet R. Kumita, Alfonso De Simone, Carlo Camilloni, Michele Vendruscolo
Article
Cell Biology
Manuela Leri, Francesco Bemporad, Reinier Oropesa-Nunez, Claudio Canale, Martino Calamai, Daniele Nosi, Matteo Ramazzotti, Sofia Giorgetti, Francesco S. Pavone, Vittorio Bellotti, Massimo Stefani, Monica Bucciantini
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2016)
Article
Biochemistry & Molecular Biology
Edoardo Del Poggetto, Angelo Toto, Chiara Aloise, Francesco Di Piro, Ludovica Gori, Francesco Malatesta, Stefano Gianni, Fabrizio Chiti, Francesco Bemporad
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Multidisciplinary Sciences
Simone Luti, Federica Martellini, Francesco Bemporad, Lorenzo Mazzoli, Paolo Paoli, Luigia Pazzagli
Editorial Material
Biochemistry & Molecular Biology
Ursula Jakob
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Denisa Jazaj, Seyyed Abolghasem Ghadami, Francesco Bemporad, Fabrizio Chiti
SCIENTIFIC REPORTS
(2019)
Article
Biochemistry & Molecular Biology
Hassan Ramshini, Reza Tayebee, Alessandra Bigi, Francesco Bemporad, Cristina Cecchi, Fabrizio Chiti
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Biochemistry & Molecular Biology
Seyyed Abolghasem Ghadami, Sean Chia, Francesco Simone Ruggeri, Georg Meisl, Francesco Bemporad, Johnny Habchi, Roberta Cascella, Christopher M. Dobson, Michele Vendruscolo, Tuomas P. J. Knowles, Fabrizio Chiti
Article
Chemistry, Medicinal
Francesco Bemporad, Manuela Leri, Matteo Ramazzotti, Massimo Stefani, Monica Bucciantini
Summary: This study investigated the interaction between oleuropein derivative OleA and TTR protein. The results showed that OleA could stabilize TTR, prevent its dissociation into monomers, and subsequent misfolding. This finding suggests the potential use of OleA in preventing degenerative diseases associated with TTR misfolding.
Article
Biochemistry & Molecular Biology
Matteo Moretti, Isabella Marzi, Cristina Cantarutti, Mirella Vivoli Vega, Walter Mandaliti, Maria Chiara Mimmi, Francesco Bemporad, Alessandra Corazza, Fabrizio Chiti
Summary: TAR DNA-binding protein 43 (TDP-43) has been associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The N-terminal domain (NTD) of TDP-43 plays a crucial role in its function and the formation of intraneuronal inclusions. The study identified an alternative conformation of NTD in the presence of SB3-10, which led to a more α-helical structure. The results also showed that the aggregation of TDP-43 was slower when pre-incubated with SB3-10, indicating the disruption of oligomeric seeds by the alternative conformation conditions. These findings provide insights into the plasticity of TDP-43 NTD and suggest strategies for monomerising TDP-43 NTD for various applications.
Article
Biochemistry & Molecular Biology
Tommaso Garfagnini, Francesco Bemporad, Daniel Harries, Fabrizio Chiti, Assaf Friedler
Summary: Hydrophobicity is a key driving force for amyloid aggregation, and the presence of osmolytes in the cellular environment has a significant impact on this process. Hydrophobic mutations can increase the aggregation rate, but osmolytes can slow down the kinetics, especially when the mutation site is closer to the center of the protein sequence.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Seyyed Abolghasem Ghadami, Francesco Bemporad, Benedetta Maria Sala, Guido Tiana, Stefano Ricagno, Fabrizio Chiti
CELLULAR AND MOLECULAR LIFE SCIENCES
(2017)
Article
Biophysics
Francesco Elia, Francesca Cantini, Fabrizio Chiti, Christopher Martin Dobson, Francesco Bemporad
BIOPHYSICAL JOURNAL
(2017)