Review
Clinical Neurology
Jared S. Katzeff, Fiona Bright, Katherine Phan, Jillian J. Kril, Lars M. Ittner, Michael Kassiou, John R. Hodges, Olivier Piguet, Matthew C. Kiernan, Glenda M. Halliday, Woojin Scott Kim
Summary: This study explores and evaluates potential biomarkers for distinguishing frontotemporal dementia and amyotrophic lateral sclerosis, aiming to improve diagnosis and treatment for patients. The two diseases share common genetic and molecular features, with a lack of sensitive and specific biomarkers for diagnostic and disease surveillance purposes.
Article
Geriatrics & Gerontology
Barbara Poletti, Federica Solca, Sabrina Maffi, Silvia Torre, Laura Carelli, Edoardo Nicolo Aiello, Roberta Ferrucci, Alberto Priori, Alessia Monti, Federico Verde, Nicola Ticozzi, Simone Migliore, Eugenia Scaricamazza, Melissa Casella, Ferdinando Squitieri, Andrea Ciammola, Vincenzo Silani
Summary: This study provides unprecedented insights into the heterogeneous semiology and determinants of apathy across ALS, PD, and HD via the Dimensional Apathy Scale (DAS), in turn informing clinical practice and research.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Alexandru Vlad Ciurea, Aurel George Mohan, Razvan-Adrian Covache-Busuioc, Horia-Petre Costin, Luca-Andrei Glavan, Antonio-Daniel Corlatescu, Vicentiu Mircea Saceleanu
Summary: Neurodegenerative diseases are a leading cause of disability and death worldwide. Recent advancements in technology and understanding, as well as the potential of gene editing, have fueled exponential growth in the field of molecular genetics. This paper aims to analyze the latest approaches in genetics and molecular sciences for four major neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. By focusing on treatment, diagnosis, and predictions, the goal is to improve analysis and identify emerging signs for better outcomes and potential novel therapies targeting specific genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Sofia Bergh, Rachel Y. Cheong, Asa Petersen, Sanaz Gabery
Summary: Neurodegenerative disorders such as HD, ALS, and FTD share commonalities in early symptoms and signs, including impairments in social cognition and psychiatric symptoms. Oxytocin (OXT) plays a crucial role in the pathology of these diseases, and understanding its signaling may reveal the underlying mechanisms of early symptoms in these disorders.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Tesfaye Wolde Tefera, Frederik J. Steyn, Shyuan T. Ngo, Karin Borges
Summary: ALS is a fatal progressive neurodegenerative disorder characterized by selective degeneration of motor neurons. There is evidence of abnormalities in energy metabolism, particularly in glucose metabolism, in ALS patients. Future investigations into modifying metabolic impairments to slow disease progression are crucial for understanding the disease and developing new therapeutic strategies.
CELL AND BIOSCIENCE
(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.
Article
Clinical Neurology
Z. Voysey, S. V. Fazal, A. S. Lazar, R. A. Barker
Summary: The research explores the intricate relationship between sleep and neurodegeneration, highlighting the significance of studying sleep abnormalities in Huntington's disease. The article discusses the current knowledge and future directions for advancing the field of sleep-neurodegeneration interface through studies in HD.
JOURNAL OF NEUROLOGY
(2021)
Article
Neurosciences
Masume Saljuqi, Peyvand Ghaderyan
Summary: The study proposes an automatic detection method for neurodegenerative diseases based on localized time-frequency information of gait signals, achieving high accuracy rates for PD, ALS, and HD detection by using sparse coefficients, a hybrid feature set, and sparse coding classifier.
NEUROSCIENCE LETTERS
(2021)
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
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
Kyle J. Trageser, Eun-Jeong Yang, Chad Smith, Ruth Iban-Arias, Tatsunori Oguchi, Maria Sebastian-Valverde, Umar Haris Iqbal, Henry Wu, Molly Estill, Md Al Rahim, Urdhva Raval, Francis J. Herman, Yong Jie Zhang, Leonard Petrucelli, Giulio Maria Pasinetti
Summary: Hexanucleotide repeat expansions in C9orf72 gene cause frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and lead to the production of toxic dipeptide repeat (DPR) proteins, with poly(glycine-arginine) (GR) being the most toxic and accumulating in relevant brain regions. Neuroinflammation is a driving factor in the disease, and increased inflammasome-mediated neuroinflammation is observed in C9orf72 FTD/ALS mice, suggesting a role for HRE in innate immunity and the NLRP3 inflammasome as a potential therapeutic target.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Yann Le Guen, Guo Luo, Aditya Ambati, Vincent Damotte, Iris Jansen, Eric Yu, Aude Nicolas, Itziar de Rojasj, Thiago Peixoto Leal, Akinori Miyashita, Celine Bellenguez, Michelle Mulan Lian, Kayenat Parveen, Takashi Morizono, Hyeonseul Park, Benjamin Grenier-Boley, Tatsuhiko Naito, Fahri Kucukali, Seth D. Talyansky, Selina Maria Yogeshwar, Vicente Sempere, Wataru Satake, Victoria Alvarez, Beatrice Arosio, Michael E. Belloy, Luisa Benussi, Anne Boland, Barbara Borroni, Maria J. Bullido, Paolo Caffarra, Jordi Clarimon, Antonio Daniele, Daniel Darling, Stephanie Debette, Jean-Francois Deleuze, Martin Dichgans, Carole Dufouil, Emmanuel During, Emrah Duzel, Daniela Galimberti, Guillermo Garcia-Ribas, Jose Maria Garcia-Alberca, Pablo Garcia-Gonzalez, Vilmantas Giedraitis, Oliver Goldhardt, Caroline Graff, Edna Grunblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Henne Holstege, Jakub Hort, Yoo Jin Jung, Deckert Jurgen, Silke Kern, Teemu Kuulasmaa, Kun Ho Lee, Ling Lin, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre de Mendonca, Merce Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gael Nicolas, Shumpei Niida, Borge G. Nordestgaard, Goran Papenberg, Janne Papma, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A. L. Pijnenburg, Gerard Pinol-Ripoll, Julius Popp, Laura Molina Porcel, Raquel Puertaj Jordi Perez-Tur, Innocenzo Rainero, Inez Ramakers, Luis M. Real, Steffi Riedel-Heller, Eloy Rodriguez-Rodriguez, Owen A. Ross, Jose Luis Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Ingmar Skoog, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John van Swieten, Raquel Sanchez-Valle, Eng-King Tan, Thomas Tegos, Charlotte Teunissen, Jesper Qvist Thomassen, Lucio Tremolizzo, Martin Vyhnalek, Frans Verhey, Margda Waern, Jens Wiltfang, Jing Zhangc, Henrik Zetterberg, Kaj Blennow, Zihuai He, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick G. Kehoe, Ole A. Andreassen, Cornelia Van Duin, Magda Tsolaki, Pascual Sanchez-Juan, Ruth Frikke-Schmidt, Kristel Sleegers, Tatsushi Todau, Anna Zettergren, Martin Ingelsson, Yukinori Okada, Giacomina Rossi, Mikko Hiltunen, Jungsoo Gim, Kouichi Ozaki, Rebecca Sims, Jia Nee Foo, Wiesje van der Fliere, Takeshi Ikeuchi, Alfredo Ramirez, Ignacio Mata, Agustin Ruiz, Ziv Gan-Or, Jean-Charles Lambert, Michael D. Greicius, Emmanuel Mignot
Summary: We analyzed the HLA associations in individuals with Parkinson's disease and Alzheimer's disease across different ancestry groups and found that these two diseases share a common protective association at the HLA locus. Fine-mapping showed that specific subtypes of HLA-DRB1*04 were responsible for this association, with HLA-DRB1*04:04 and HLA-DRB1*04:07 showing the strongest association. This protective effect was also associated with decreased neurofibrillary tangles in the brain and reduced levels of tau protein in cerebrospinal fluid.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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.
Editorial Material
Multidisciplinary Sciences
Zak Doric, Ken Nakamura
Summary: By disrupting mitochondria in vulnerable neuronal cells, mice provide a new model of Parkinson's disease that challenges long-held ideas about the disease's motor symptoms.
Article
Clinical Neurology
Arpan R. Mehta, Jenna M. Gregory, Owen Dando, Roderick N. Carter, Karen Burr, Jyoti Nanda, David Story, Karina McDade, Colin Smith, Nicholas M. Morton, Don J. Mahad, Giles E. Hardingham, Siddharthan Chandran, Bhuvaneish T. Selvaraj
Summary: The study found that axonal dysfunction in C9orf72-ALS patients is associated with shorter axons, impaired mitochondrial transport, and altered mitochondrial bioenergetics, indicating that mitochondrial dysfunction is a key factor in axonal dysfunction. Increasing mitochondrial biogenesis through genetic manipulation can correct the bioenergetic deficit and rescue axonal length and transport phenotypes.
ACTA NEUROPATHOLOGICA
(2021)
Article
Clinical Neurology
Mootaz M. Salman, Philip Kitchen, Andrea Halsey, Marie Xun Wang, Susanna Tornroth-Horsefield, Alex C. Conner, Jerome Badaut, Jeffrey J. Iliff, Roslyn M. Bill
Summary: AQP4 plays a crucial role in the central nervous system, regulating water exchange, cell volume, and astrocyte migration, and is associated with glymphatic function and neurodegenerative diseases.
Article
Biochemistry & Molecular Biology
Hiroaki Ishida, Hans J. Vogel, Alex C. Conner, Philip Kitchen, Roslyn M. Bill, Justin A. MacDonald
Summary: This study assessed the CaM-binding properties of AQP4, finding two putative CaM-binding domains in the cytoplasmic regions. The N-terminal CBD of AQP4 interacted predominantly with the N-lobe of CaM, while the C-terminal AQP4 peptide interacted with both the C-and N-lobes of CaM. The data support a unique adapter protein binding mode for CaM with AQP4.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Review
Biochemistry & Molecular Biology
Kim Wagner, Lucas Unger, Mootaz M. Salman, Philip Kitchen, Roslyn M. Bill, Andrea J. Yool
Summary: This review highlights the key roles of aquaporins (AQPs) in fluid homeostasis, glandular secretions, signal transduction and sensation, barrier function, immunity and inflammation, cell migration, and angiogenesis. It emphasizes that the functions of AQPs are more complex than simply mediating the flow of water. Further research and development of AQP inhibitors will provide new insights and treatments for AQP-associated disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Benjamin O. Ezema, Kingsley O. Omeje, Roslyn M. Bill, Alan D. Goddard, Sabinus Oscar O. Eze, Alfred Fernandez-Castane
Summary: Lipolytic fungus Aspergillus flavus was isolated, and its lipase gene was sequenced and characterized. The study revealed the presence of a lipase consensus sequence and a catalytic active site lid domain in the Aspergillus flavus lipase sequence. Furthermore, the study provided insights into the structural and molecular properties of the lipase, which will be crucial for future biotechnology applications.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Pharmacology & Pharmacy
Mootaz M. Salman, Philip Kitchen, Andrea J. Yool, Roslyn M. Bill
Summary: Aquaporins play a role in various pathological conditions, and recent research has identified potential routes for inhibiting their function as a new drug development strategy. Developing new drug development frameworks for conditions associated with disrupted water and solute homeostasis will help meet the urgent clinical needs of millions of patients.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2022)
Correction
Oncology
Jomnarong Lertsuwan, Kornkamon Lertsuwan, Anyaporn Sawasdichai, Nathapol Tasnawijitwong, Ka Ying Lee, Philip Kitchen, Simon Afford, Kevin Gaston, Padma-Sheela Jayaraman, Jutamaad Satayavivad
Article
Clinical Neurology
Emma M. J. Passchier, Sven Kerst, Eelke Brouwers, Eline M. C. Hamilton, Quinty Bisseling, Marianna Bugiani, Quinten Waisfisz, Philip Kitchen, Lucas Unger, Marjolein Breur, Leoni Hoogterp, Sharon de Vries, Truus E. M. Abbink, Maarten H. P. Kole, Rob Leurs, Henry F. Vischer, Maria S. Brignone, Elena Ambrosini, Francois Feillet, Alfred P. Born, Leon G. Epstein, Huibert D. Mansvelder, Rogier Min, Marjo S. van der Knaap
Summary: Brain oedema is a life-threatening complication of various neurological conditions. Understanding molecular mechanisms of brain volume regulation is critical for therapy development. We performed genetic studies to identify novel gene variants in MLC patients, diagnosed by clinical and MRI features, without MLC1 or GLIALCAM variants. We identified aquaporin-4 and GPRC5B as old and new players in genetic brain oedema, shedding light on the protein complex involved in astrocyte volume regulation and identifying GPRC5B as a novel potentially druggable target for treating brain oedema.
Article
Neurosciences
Shaline V. Fazal, Clara Mutschler, Civia Z. Chen, Mark Turmaine, Chiung-Ya Chen, Yi-Ping Hsueh, Andrea Ibanez-Grau, Andrea Loreto, Angeles Casillas-Bajo, Hugo Cabedo, Robin J. M. Franklin, Roger A. Barker, Kelly R. Monk, Benjamin J. Steventon, Michael P. Coleman, Jose A. Gomez-Sanchez, Peter Arthur-Farraj
Summary: Since SARM1 mutations have been identified in human neurological disease, inhibiting SARM1 has become an attractive therapeutic strategy to preserve axons. However, it is still unknown whether SARM1 is present and functional in myelinating glia. This study finds that oligodendrocytes express SARM1 and its activation results in cell death, while peripheral glia (Schwann cells) likely contain no functionally relevant levels of SARM1.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Materials Science, Multidisciplinary
Ibtihal Haitham Gani, Zaid Al-Obaidi
Summary: In this study, novel pyridin-3-yl-pyrimidin-2-yl-aminophenyl-amide derivatives were synthesized using two methods, trimethylamine and magnesium oxide nanoparticles. The synthesized compounds were evaluated for their biological activities including receptor tyrosine kinase inhibition, anticancer activity against lung cancer, antibacterial and antifungal activity against specialized bacterial and fungal species, and antioxidant activity. The results showed that the compounds exhibited higher cytotoxic activity than imatinib. Derivative IIB showed the lowest IC50 value against lung cancer cell lines, and derivative IIC exhibited the highest antibacterial and antifungal activity. Moreover, the derivatives showed antioxidant activity comparable to ascorbic acid.
FRONTIERS IN MATERIALS
(2023)
Article
Biotechnology & Applied Microbiology
Hung M. Nguyen, Loan Q. Le, Luca Sella, Luke M. Broadbent, Roslyn M. Bill, Van V. Vu
Summary: This study successfully expressed MoAA16 heterologously in Pichia pastoris and revealed its cellulose-active PMO properties. MoAA16 can break down cellulose through oxidation and enhance cellulase hydrolysis, resulting in the production of more monosaccharide products. These findings highlight the potential of MoAA16 for applications in biofuel production and chemical synthesis.
ELECTRONIC JOURNAL OF BIOTECHNOLOGY
(2023)
Review
Neurosciences
Qasim M. Alhadidi, Ghaith A. Bahader, Oiva Arvola, Philip Kitchen, Zahoor A. Shah, Mootaz M. Salman
Summary: Astrocytes play a crucial role in regulating neuronal plasticity after central nervous system (CNS) injuries, with both pathogenic and protective effects. While there is extensive research on the negative consequences of astrocyte proliferation following brain injuries, there is a growing interest in exploring the potential protective functions of astrocytes and their contribution to chronic functional recovery. This review discusses the protective functions of astrocytes in aspects such as edema, inflammation, and blood-brain barrier dysfunction, as well as their role in tissue regeneration.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Materials Science, Multidisciplinary
Gheith M. Alasadi, Zaid Al-Obaidi
Summary: Nowadays, various factors contribute to the resistance of microbes to antibiotics, with irrational antibiotic use being a notable example. Therefore, the synthesis and reporting of heterocyclic compounds with multiple biological properties are highly valuable. This study focused on the synthesis and characterization of new derivatives of the antibiotic Ciprofloxacin, evaluating their in vitro anticancer and antimicrobial activities using various methods such as MTT and CLSI instructions.
FRONTIERS IN MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Andrea Markou, Philip Kitchen, Ahmed Aldabbagh, Mariaelena Repici, Mootaz M. Salman, Roslyn M. Bill, Zita Balklava
Summary: The AQP4 water channel plays a crucial role in brain swelling following insults like traumatic injury or stroke, with its trafficking mechanisms involving early and recycling endosomes as well as cytoskeleton dynamics. AQP4 constantly cycles between the cell surface and intracellular vesicles in mammalian cells, with internalisation being dynamin-dependent. Targeting Rab5, Rab11, and cytoskeleton dynamics could provide potential avenues for edema treatment.
JOURNAL OF NEUROCHEMISTRY
(2023)
