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).
Article
Neurosciences
Panlin Liao, Yanchun Yuan, Zhen Liu, Xiaorong Hou, Wanzhen Li, Jin Wen, Kexuan Zhang, Bin Jiao, Lu Shen, Hong Jiang, Jifeng Guo, Beisha Tang, Zhuohua Zhang, Zhonghua Hu, Junling Wang
Summary: This study identified rare damage variants (RDVs) in the KIF1A gene associated with ALS and delineated the clinical characteristics of ALS patients with KIF1A RDVs. The majority of these variants are located at the C-terminal cargo-binding region of the KIF1A protein and enhance the binding of specific vesicles. KIF1A is highlighted as an important player in the pathogenesis of ALS.
TRANSLATIONAL NEURODEGENERATION
(2022)
Review
Neurosciences
Frances Theunissen, Phillip K. West, Samuel Brennan, Bojan Petrovic, Kosar Hooshmand, P. Anthony Akkari, Matt Keon, Boris Guennewig
Summary: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective early degeneration of motor neurons in the brain and spinal cord. The integrity of the cytoskeleton and mitochondria of motor neurons plays a crucial role in maintaining axonal stability, transport, and signaling between neurons. The formation of protein aggregates and mitochondrial dysfunction are shared pathological features in ALS, Alzheimer's disease, Parkinson's disease, Huntington's disease, and Charcot-Marie-Tooth disease.
TRANSLATIONAL NEURODEGENERATION
(2021)
Review
Biochemistry & Molecular Biology
Elisa Duranti, Chiara Villa
Summary: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive loss of motor neurons (MNs) in the brain and spinal cord. The aggregation and accumulation of ubiquitinated protein inclusions in degenerating MNs are key pathological features of ALS. Recent research has provided insights into the molecular mechanisms underlying protein aggregate accumulation in ALS, which may aid in the development of therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Mohamed F. Elmansy, Cory T. Reidl, Mizzanoor Rahaman, P. Hande Ozdinler, Richard B. Silverman
Summary: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects the motor neurons in the brain and spinal cord. Despite the approval of three drugs, there is still a need for better treatment strategies. Various approaches, including targeting genetic mutations and reducing oxidative stress, have been explored. Additionally, repurposing previously identified drugs has also been studied. This review discusses drug discovery efforts targeting cellular pathologies caused by genetic mutations in ALS and offers recommendations for more effective ALS drug discovery.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Neurosciences
Guangnan Peng, Ao Gu, Hongyan Niu, Linlin Chen, Yan Chen, Miaojin Zhou, Yiti Zhang, Jie Liu, Licong Cai, Desheng Liang, Xionghao Liu, Mujun Liu
Summary: UBQLN2 colocalizes with SG component proteins G3BP1, TIA-1, ATXN2, and PABPC1, participating in regulating SG dynamics. UBQLN2 mutation affects stress granule assembly by regulating TIA-1. Moreover, overexpression of UBQLN2 P497H mutant inhibits 4E-BP1 phosphorylation and affects TDP-43's nuclear and cytoplasmic distribution.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Neurosciences
Sarah Mueller, Lorena Decker, Sonja Menge, Albert C. C. Ludolph, Axel Freischmidt
Summary: This review article introduces the roles of FMR1, FXR1, and FXR2 in neurodevelopmental disorders and amyotrophic lateral sclerosis (ALS), and discusses their potential contribution to disease mechanisms and feasibility as therapeutic targets.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Kyle R. Christensen, Benjamin Combs, Collin Richards, Tessa Grabinski, Mohammed M. Alhadidy, Nicholas M. Kanaan
Summary: Our understanding of the tau protein's role as a scaffolding protein involved in signaling regulation has implications for Alzheimer's disease and other tauopathies. Pseudophosphorylation of tau disrupts normal axonal transport through a PP1-dependent pathway. Interaction between tau and PP1 gamma, as well as tau phosphorylation at S199-T205, leads to axonal transport impairment.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Belgin Sever, Halilibrahim Ciftci, Hasan DeMirci, Hilal Sever, Firdevs Ocak, Burak Yulug, Hiroshi Tateishi, Takahisa Tateishi, Masami Otsuka, Mikako Fujita, Ayse Nazli Basak
Summary: Amyotrophic lateral sclerosis (ALS) is a rapidly debilitating neurodegenerative disorder with limited treatment options. Recent studies have identified multiple pathological mechanisms, including oxidative stress, mitochondrial dysfunction, and excitotoxicity, providing potential directions for future ALS treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Greta Grassmann, Mattia Miotto, Lorenzo Di Rienzo, Federico Salaris, Beatrice Silvestri, Elsa Zacco, Alessandro Rosa, Gian Gaetano Tartaglia, Giancarlo Ruocco, Edoardo Milanetti
Summary: This article investigates the protein aggregation process in ALS, providing a computational model of interaction based on the evaluation of shape complementarity at the molecular interfaces. The study proposes and assesses possible association mechanisms between CTFs, and performs molecular docking and additional MD simulations to propose possible complexes and evaluate their stability, focusing on high shape complementarity and involvement of beta 3 and beta 5 strands at the interfaces.
Review
Neurosciences
Xiaoman Yang, Zhuoran Ma, Piaopiao Lian, Yan Xu, Xuebing Cao
Summary: Many neurodegenerative diseases are characterized by the accumulation of pathogenic proteins and abnormal organelle localization, which are likely due to axonal transport deficits. This review investigated mechanisms underlying the development of axonal transport deficits in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease. These mechanisms include changes in motor proteins, microtubules, and cargoes. Further research is needed to determine disease-specific axonal transport defects and their suitability as therapeutic targets.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Clinical Neurology
Linjing Zhang, Tuo Ji, Chujun Wu, Shuo Zhang, Lu Tang, Nan Zhang, Xiangyi Liu, Dongsheng Fan
Summary: This study found a positive correlation between serum NfL levels and the severity of axonal degeneration of lower motor neurons (LMNs) in the early symptomatic phase of amyotrophic lateral sclerosis (ALS), especially in patients with signs of predominant LMN involvement. These results have important implications for patient selection and monitoring treatment efficacy in future disease-modifying clinical trials.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biology
Tien-Ying Tsai, Chun-Yu Chen, Tien-Wei Lin, Tien-Chang Lin, Feng-Lan Chiu, Orion Shih, Yu-Chun Lin, An-Chung Su, Chiung-Mei Chen, U-Ser Jeng, Hung-Chih Kuo, Chi-Fon Chang, Yun-Ru Chen
Summary: This study reveals the molecular mechanism of SERF1a and mutant Httex1 in facilitating therapeutic development for Huntington's disease. SERF1a induces aggregation of mutated TrxHttex1 through α-helical regions, leading to the formation of β-sheet enriched conformation, exacerbating polyQ-induced toxicity. The interaction between SERF1a and Httex1 is intensified by enhancing α-helical content.
COMMUNICATIONS BIOLOGY
(2023)
Review
Neurosciences
Honglu Yu, Min Xiong, Zhentao Zhang
Summary: Neurodegenerative diseases pose a growing threat to the health of elderly individuals worldwide. These diseases share multiple cellular and molecular mechanisms. Glycogen synthase kinase-3 beta (GSK-3β) plays a significant role in the pathogenesis of these diseases and may serve as a therapeutic target.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Katelyn M. Baumer, Christopher D. Cook, Collin T. Zahler, Alexandra A. Beard, Zhijuan Chen, Jordan C. Koone, Chad M. Dashnaw, Raul A. Villacob, Touradj Solouki, John L. Wood, David R. Borchelt, Bryan F. Shaw
Summary: Repulsive electrostatic forces between prion-like proteins hinder aggregation, but compounds selectively boosting the negative charge of misfolded SOD1 were synthesized. These compounds showed slower aggregation of acetylated amyloid-SOD1 compared to unacetylated forms, and exhibited reactivity with other types of proteins.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Radiology, Nuclear Medicine & Medical Imaging
Rodolfo Gabriel Gatto, Carina Weissmann
CURRENT MEDICAL IMAGING
(2019)
Review
Neurosciences
Osvaldo D. Uchitel, Carlota Gonzalez Inchauspe, Carina Weissmann
Review
Clinical Neurology
Roland Brandt, Nataliya I. Trushina, Lidia Bakota
FRONTIERS IN NEUROLOGY
(2020)
Article
Geriatrics & Gerontology
Rodolfo G. Gatto, Carina Weissmann, Manish Amin, Quetzalli D. Angeles-Lopez, Lucia Garcia-Lara, Libia C. Salinas Castellanos, Daniel Deyoung, Jose Segovia, Thomas H. Mareci, Osvaldo D. Uchitel, Richard L. Magin
Summary: This study aims to comprehensively analyze early microstructural changes in Huntington's disease (HD) using ultra-high field diffusion MRI techniques and evaluate their association with cellular biomarkers of neuroinflammation. The study found that dMRI can extract non-invasive information of neuropathological events in the early stages of HD, and the combination of multiple imaging techniques is beneficial for early diagnosis and neuromonitoring.
NEUROBIOLOGY OF AGING
(2021)
Review
Cell Biology
Rodolfo G. Gatto, Carina Weissmann
Summary: In recent decades, advances in research on genetic, cellular, and microstructural changes associated with Huntington's disease (HD) have improved our understanding of this progressive and fatal illness. Ultra-high field diffusion MRI (UHFD-MRI) techniques offer a more comprehensive analysis of early microstructural changes and their potential link to histological biomarkers. Combining qualitative studies with UHFD-MRI in animal models can provide insights into early neuropathological events, neuroinflammation, and brain repair mechanisms. The combination of diffusion MRI imaging techniques and complex neuropathological analysis could lead to the discovery of new imaging biomarkers and early diagnosis and neuromonitoring of HD patients.
NEURAL REGENERATION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Christian Conze, Marina Rierola, Nataliya Trushina, Michael Peters, Dennis Janning, Max Holzer, Jurgen J. Heinisch, Thomas Arendt, Lidia Bakota, Roland Brandt
Summary: Tau protein plays a central role in diseases like Alzheimer's, and its function can be affected by cellular senescence. In this study, researchers found that a specific form of tau protein (TauC3) is increased in senescent mice and AD patients. This modified tau protein has reduced dynamics in interacting with microtubules, which leads to defects in axonal transport and neuronal degeneration. The microtubule-targeting drug Epothilone D can normalize this interaction and modulate transport processes. These findings suggest the potential of using microtubule-targeting drugs to restore the physiological function of tau protein.
MOLECULAR PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Libia Catalina Salinas Castellanos, Rodolfo Gabriel Gatto, Silvia Adriana Menchon, Matias Blaustein, Osvaldo Daniel Uchitel, Carina Weissmann
Summary: The study describes a simple method involving a tabletop centrifuge and different detergents to obtain cell fractions enriched in proteins from different cell compartments. This method can be used to identify transmembrane proteins and membrane-embedded or weakly associated proteins, requiring only a small amount of cell material and typical laboratory equipment.
Article
Neurosciences
Christian Conze, Nataliya Trushina, Michael Holtmannspoetter, Marina Rierola, Simone Attanasio, Lidia Bakota, Jacob Piehler, Roland Brandt
Summary: Microtubules play a crucial role in the development and structural regulation of neurons. Super-resolution imaging combined with algorithm-based analysis allows for quantitative assessment of microtubule organization in neuronal processes. Treatment with the microtubule-targeting drug EpoD increases microtubule density and shortens their length distribution.
BRAIN RESEARCH BULLETIN
(2022)
Article
Chemistry, Medicinal
Maria Natalia Gobetto, Libia Catalina Salinas Castellanos, Natalia Estefania Contreras, Alejandro Omar Sodero, Damian Alejandro Cambiagno, Georgina Oriana Mingolo Malnati, Mayra Micaela Montes, Osvaldo Daniel Uchitel, Carina Weissmann
Summary: This study highlights the important role of ASIC1 in pain, especially in both phases of the formalin test. After formalin injection, ASIC1 levels increased and showed different distributions in various brain regions and spinal cord levels. In addition, gender differences were observed in the ACC.
Review
Biochemistry & Molecular Biology
Anna-Carina Soehnel, Roland Brandt
Summary: Stress granules are cellular RNA-protein complexes that form in response to stressors, increasing the concentration of RNA and protein and modulating mRNA availability for translation. Neuronal stress granules function as dynamic cytosolic microcompartments, with components cycling in and out to monitor the cellular environment. They have distinctive features, contain substructures with transient interactions, and modulate protein expression and the proteoform profile of tau. Understanding the regulation of stress granule dynamics and their material state in neurons is crucial for understanding their function in stress responses.
BIOLOGICAL CHEMISTRY
(2023)
Review
Neurosciences
Carina Weissmann, Adriana A. Albanese, Natalia E. Contreras, Maria N. Gobetto, Libia C. Salinas Castellanos, Osvaldo D. Uchitel
Summary: Fabry disease is a genetic disorder characterized by neuropathic pain, and the underlying mechanisms of pain are still unclear. Advancements in understanding the pain mechanism may lead to improved therapies, and the development of preclinical models has accelerated research in neuropathy.
Article
Biochemistry & Molecular Biology
Libia Catalina Salinas Castellanos, Paula Rozenfeld, Rodolfo Gabriel Gatto, Ricardo Claudio Reisin, Osvaldo Daniel Uchitel, Carina Weissmann
NEUROCHEMISTRY INTERNATIONAL
(2020)
Article
Biochemistry & Molecular Biology
Rodolfo G. Gatto, Carina Weissmann, Manish Amin, Ariel Finkielsztein, Ronen Sumagin, Thomas H. Mareci, Osvaldo D. Uchitel, Richard L. Magin
ANIMAL MODELS AND EXPERIMENTAL MEDICINE
(2020)
Article
Neurosciences
Mariya Hrynchak, Marina Rierola, Nataliya Golovyashkina, Lorene Penazzi, Wiebke C. Pump, Bastian David, Frederik Suendermann, Roland Brandt, Lidia Bakota
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2020)
Article
Neurosciences
Carolina Ortiz-Sanz, Adhara Gaminde-Blasco, Jorge Valero, Lidia Bakota, Roland Brandt, Jose L. Zugaza, Carlos Matute, Elena Alberdi
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2020)