Review
Cell Biology
Brittani R. Price, Lance A. Johnson, Christopher M. Norris
Summary: Astrocyte reactivity is a key feature of neuroinflammation in Alzheimer's disease and other neurodegenerative conditions, with roles extending beyond classic inflammatory processes to include synapse function, brain metabolism, neurovascular coupling, and sleep/wake patterns. Understanding astrocyte signaling is leading to new drug targets and treatment approaches for dementia, potentially reshaping our understanding of AD pathophysiology.
AGEING RESEARCH REVIEWS
(2021)
Article
Biology
Rene Solano Fonseca, Patrick Metang, Nathan Egge, Yingjian Liu, Kielen R. Zuurbier, Karthigayini Sivaprakasam, Shawn Shirazi, Ashleigh Chuah, Sonja L. B. Arneaud, Genevieve Konopka, Dong Qian, Peter M. Douglas
Summary: Concussion, a type of traumatic brain injury, can increase the risk of developing Alzheimer's and Parkinson's disease. Studies suggest that different types of brain cells, including neurons and astrocytes, may be damaged during a concussion, with astrocytes potentially playing a protective role in preserving dopaminergic neurons. The balance of energy production and metabolism in brain cells, particularly in response to trauma, may be crucial in preventing cell death and neurodegeneration.
Article
Neurosciences
Alice Filippini, Veronica Mutti, Gaia Faustini, Francesca Longhena, Ileana Ramazzina, Federica Rizzi, Alice Kaganovich, Dorien A. Roosen, Natalie Landeck, Megan Duffy, Isabella Tessari, Federica Bono, Chiara Fiorentini, Elisa Greggio, Luigi Bubacco, Arianna Bellucci, Mariacristina Missale, Mark R. Cookson, Massimo Gennarelli, Isabella Russo
Summary: The progressive neuropathological damage in Parkinson's disease is believed to be related to the spread of aggregated forms of alpha-synuclein. Clearance of extracellular alpha-synuclein by neurons may be a key mechanism to control its concentration. Clusterin, a glycoprotein associated with Alzheimer's disease, interacts with alpha-synuclein aggregates and limits their uptake by astrocytes, which may contribute to the spreading of Parkinson's pathology.
Article
Biochemistry & Molecular Biology
Kelby M. Killoy, Mariana Pehar, Benjamin A. Harlan, Marcelo R. Vargas
Summary: This study identified altered expression of clock genes in mutant ALS mouse models and astrocytes from ALS patients, suggesting disrupted communication between the suprachiasmatic nucleus and peripheral tissues. These changes may contribute to metabolic and redox imbalance in ALS, providing potential targets for disease-modifying interventions.
Review
Neurosciences
Jill M. M. Lawrence, Kayla Schardien, Brian Wigdahl, Michael R. R. Nonnemacher
Summary: In the contexts of aging, injury, or neuroinflammation, activated microglia induce neurotoxic astrocytes that downregulate supportive functions and secrete neurotoxic factors, complement components, and chemokines, which may facilitate immune cell recruitment. The proportion of pro-inflammatory reactive astrocytes increases with age and is particularly abundant in neurodegenerative disorders. As the identification of astrocyte phenotypes progress, their molecular and cellular effects are characterized in a growing array of neuropathologies.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Editorial Material
Clinical Neurology
Charles Bernick, Guogen Shan, Aaron Ritter, Nicholas J. Ashton, Kaj Blennow, Juan Lantero-Rodriguez, Anniina Snellman, Henrik Zetterberg
Summary: This study investigates the relationship between blood biomarkers and cognitive function and brain volumes in professional fighters. The results suggest that longitudinal plasma GFAP levels may play a role in identifying individuals at risk of progressive brain atrophy and cognitive decline.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Immunology
Michael MacLean, Judyta Juranek, Swetha Cuddapah, Raquel Lopez-Diez, Henry H. Ruiz, Jiyuan Hu, Laura Frye, Huilin Li, Paul F. Gugger, Ann Marie Schmidt
Summary: The study demonstrates the significant role of microglia RAGE in the progression of ALS pathology, showing that microglia Ager deletion can extend survival in male SOD1(G93A) mice and ameliorate certain pathways identified in human ALS patients.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Biochemistry & Molecular Biology
Muhammad Ali Haidar, Zaynab Shakkour, Chloe Barsa, Maha Tabet, Sarin Mekhjian, Hala Darwish, Mona Goli, Deborah Shear, Jignesh D. Pandya, Yehia Mechref, Riyad El Khoury, Kevin Wang, Firas Kobeissy
Summary: This study investigated the protective effects of MitoQ in traumatic brain injury using a mouse model. The results showed that MitoQ improved neurological and cognitive functions, reduced inflammation, and prevented axonal injury.
Article
Biochemistry & Molecular Biology
Mariana Bresque, Daniel Esteve, Mariana Pehar, Marcelo R. Vargas
Summary: NAD(+) metabolism plays a significant role in neuronal function and its dysregulation is associated with neurological disorders. Modulating NAD(+) availability could be a promising therapeutic approach for these disorders.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Review
Geriatrics & Gerontology
Leonard Radu Pinosanu, Bogdan Capitanescu, Daniela Glavan, Sanziana Godeanu, Israel Fernaundez Cadenas, Thorsten R. Doeppner, Dirk M. Hermann, Adrian-Tudor Balseanu, Catalin Bogdan, Aurel Popa-Wagner
Summary: The functions and activities of astroglia cells in brain development, aging, and neurodegenerative diseases differ. Comparing the transcriptomic activity of astroglia cells in these processes may provide new therapeutic strategies to protect the aging brain and improve clinical outcomes.
Article
Multidisciplinary Sciences
Robin Bishop, Seok Joon Won, Karen-Amanda Irvine, Jayinee Basu, Eric S. Rome, Raymond A. Swanson
Summary: Blast exposure can lead to brain injuries through multiple mechanisms, and axonal injury is a major type of injury that is independent of head movement. Especially, axons in the cerebellar white matter are particularly vulnerable to blast exposure.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Jung Yeon Hong, Mi Na Kim, Eun Gyul Kim, Jae Woo Lee, Hye Rin Kim, Soo Yeon Kim, Soon Min Lee, Yoon Hee Kim, Kyung Won Kim, Myung Hyun Sohn
Summary: Exposure to high oxygen concentrations leads to excessive generation of reactive oxygen species, causing cellular injury and multiple organ dysfunctions. Clusterin (CLU) expression is increased during prolonged hyperoxia-induced lung injury, and replenishment of CLU can alleviate hyperoxia-induced cell death.
Review
Cell Biology
Nadia D'Ambrosi, Martina Milani, Savina Apolloni
Summary: S100A4, a member of the S100 protein family, plays diverse roles in different cellular contexts; while it has been primarily associated with tumorigenesis and metastasis, it also plays a key role in promoting inflammation in various organs; in the nervous system, S100A4 contributes to neurogenesis, cellular motility, and inflammatory responses.
Review
Biochemistry & Molecular Biology
Ying Chen, John Man Tak Chu, Raymond Chuen Chung Chang, Gordon Tin Chun Wong
Summary: The complement system plays a crucial role in the central nervous system beyond immunity, impacting neurodevelopment and neurodegenerative diseases. Proper activation of the complement system is essential for maintaining normal brain function, but overactivation or dysregulation may lead to synaptic dysfunction and excessive pro-inflammatory responses. Targeting complement factors shows therapeutic potential for neurodegenerative conditions.
Review
Biochemistry & Molecular Biology
Stefania Della Vecchia, Maria Marchese, Filippo Maria Santorelli
Summary: This study systematically reviewed the role of glial cells in Lafora disease (LD). The findings suggest that glial cells accumulate polyglucosan bodies (PBs) in LD and contribute to neurodegeneration and epilepsy. Future research should consider glial cells as a potential therapeutic target.
Article
Biochemistry & Molecular Biology
Youn-Bok Lee, Emma L. Scotter, Do-Young Lee, Claire Troakes, Jacqueline Mitchell, Boris Rogelj, Jean-Marc Gallo, Christopher E. Shaw
Summary: This study investigates the role of cytoplasmic TDP-43 in stress granule formation and response to stress, with findings suggesting that TDP-43 relocalizes to the cytoplasm through different mechanisms under different stress conditions. Additionally, the study demonstrates that relocalization of TDP-43 induces PARP cleavage, leading to cellular toxicity, and reveals changes in other cytoplasmic structures during stress recovery.
HUMAN MOLECULAR GENETICS
(2022)
Article
Oncology
Sandra Gray-Rodriguez, Melanie P. Jensen, Maria Otero-Jimenez, Brian Hanley, Olivia C. Swann, Patrick A. Ward, Francisco J. Salguero, Nadira Querido, Ildiko Farkas, Elisavet Velentza-Almpani, Justin Weir, Wendy S. Barclay, Miles W. Carroll, Zane Jaunmuktane, Sebastian Brandner, Ute Pohl, Kieren Allinson, Maria Thom, Claire Troakes, Safa Al-Sarraj, Magdalena Sastre, Djordje Gveric, Steve Gentleman, Candice Roufosse, Michael Osborn, Javier Alegre-Abarrategui
Summary: This study comprehensively validates and analyzes the organ tropism of SARS-CoV-2 at the histological level. The findings demonstrate the widespread involvement of the respiratory, digestive, haematopoietic, genitourinary, and nervous systems. The results provide important insights into the transmission and pathogenic mechanisms of the virus.
JOURNAL OF PATHOLOGY
(2022)
Article
Clinical Neurology
Benjamin G. Trist, Sian Genoud, Stephane Roudeau, Alexander Rookyard, Amr Abdeen, Veronica Cottam, Dominic J. Hare, Melanie White, Jens Altvater, Jennifer A. Fifita, Alison Hogan, Natalie Grima, Ian P. Blair, Kai Kysenius, Peter J. Crouch, Asuncion Carmona, Yann Rufin, Stephane Claverol, Stijn Van Malderen, Gerald Falkenberg, David J. Paterson, Bradley Smith, Claire Troakes, Caroline Vance, Christopher E. Shaw, Safa Al-Sarraj, Stuart Cordwell, Glenda Halliday, Richard Ortega, Kay L. Double
Summary: This study examined the changes in SOD1 protein in post-mortem spinal cord tissues of ALS patients. The results showed mislocalization and accumulation of SOD1 protein in motor neurons of ALS patients, which was associated with instability and mismetallation of enzymatically active SOD1 dimers, as well as alterations to SOD1 post-translational modifications and molecular chaperones governing SOD1 maturation. These changes mostly occurred in regions of neurodegeneration and differentiated ALS patients from controls effectively.
Article
Medicine, Legal
Safa Al-Sarraj, Claire Troakes, Guy N. Rutty
Summary: This study investigates whether axonal injury can be detected in patients who died rapidly after TBI in a period of less than 30 minutes through beta APP staining. The results suggest that axonal injury can be detected in this group of patients, which is helpful in diagnosing severe TBI.
INTERNATIONAL JOURNAL OF LEGAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Nicolai Franzmeier, Matthias Brendel, Leonie Beyer, Luna Slemann, Gabor G. Kovacs, Thomas Arzberger, Carolin Kurz, Gesine Respondek, Milica J. Lukic, Davina Biel, Anna Rubinski, Lukas Frontzkowski, Selina Hummel, Andre Muller, Anika Finze, Carla Palleis, Emanuel Joseph, Endy Weidinger, Sabrina Katzdobler, Mengmeng Song, Gloria Biechele, Maike Kern, Maximilian Scheifele, Boris-Stephan Rauchmann, Robert Perneczky, Michael Rullman, Marianne Patt, Andreas Schildan, Henryk Barthel, Osama Sabri, Jost J. Rumpf, Matthias L. Schroeter, Joseph Classen, Victor Villemagne, John Seibyl, Andrew W. Stephens, Edward B. Lee, David G. Coughlin, Armin Giese, Murray Grossman, Corey T. McMillan, Ellen Gelpi, Laura Molina-Porcel, Yaroslau Compta, John C. van Swieten, Laura Donker Laat, Claire Troakes, Safa Al-Sarraj, John L. Robinson, Sharon X. Xie, David J. Irwin, Sigrun Roeber, Jochen Herms, Mikael Simons, Peter Bartenstein, Virginia M. Lee, John Q. Trojanowski, Johannes Levin, Gunter Hoeglinger, Michael Ewers
Summary: The present study combines tau-PET, resting-state fMRI, and histopathology data to demonstrate the association between brain connectivity and tau deposition patterns in 4-repeat tauopathies.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Kamar E. Ameen-Ali, Abigail Bretzin, Edward B. Lee, Rebecca Folkerth, Lili-Naz Hazrati, Diego Iacono, C. Dirk Keene, Julia Kofler, Gabor G. Kovacs, Amber Nolan, Daniel P. Perl, David S. Priemer, Douglas H. Smith, Douglas J. Wiebe, William Stewart
Summary: This study evaluated the neuropathological changes of chronic traumatic encephalopathy (CTE) and found that the presence of both neuronal and astroglial tau pathologies facilitates the detection of CTE, while the detection is less consistent when only neuronal pathology is visible.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Milica Jecmenica Lukic, Gesine Respondek, Carolin Kurz, Yaroslau Compta, Ellen Gelpi, Leslie W. Ferguson, Alex Rajput, Claire Troakes, John C. van Swieten, Armin Giese, Sigrun Roeber, Jochen Herms, Thomas Arzberger, Guenter Hoeglinger
Summary: The aim of this study was to identify the clinical characteristics and neuropathological determinants of a subgroup of benign progressive supranuclear palsy with particularly long disease duration. The findings showed that a considerable proportion of patients had a disease duration of >= 10 years, and the absence of ocular motor abnormalities within the first 3 years from disease onset was the only significant clinical predictor of longer survival. The distribution of neurodegeneration parameters and astrocytic tau pathology differed between patients with longer survival and those with shorter survival. These findings have important implications for understanding the progression mechanisms of progressive supranuclear palsy.
ANNALS OF NEUROLOGY
(2022)
Article
Clinical Neurology
Andrew King, Yuan Kai Lee, Shalmai Jones, Claire Troakes
Summary: This study reports a rare case of a patient with combined ALS-C9orf72 and multiple system atrophy (MSA). Initially misdiagnosed with Parkinson's disease, the patient was later confirmed through pathological examination to have ALS and C9orf72 repeat expansion. This case highlights the complexity and overlapping features of neurodegenerative diseases.
Article
Clinical Neurology
Franziska Hopfner, Anja K. Tietz, Viktoria C. Ruf, Owen A. Ross, Shunsuke Koga, Dennis Dickson, Adriano Aguzzi, Johannes Attems, Thomas Beach, Allison Beller, William P. Cheshire, Vivianna van Deerlin, Paula Desplats, Guenther Deuschl, Charles Duyckaerts, David Ellinghaus, Valentin Evsyukov, Margaret Ellen Flanagan, Andre Franke, Matthew P. Frosch, Marla Gearing, Ellen Gelpi, Jay A. van Gerpen, Bernardino Ghetti, Jonathan D. Glass, Lea T. Grinberg, Glenda Halliday, Ingo Helbig, Matthias Hollerhage, Inge Huitinga, David John Irwin, Dirk C. Keene, Gabor G. Kovacs, Edward B. Lee, Johannes Levin, Maria J. Marti, Ian Mackenzie, Ian McKeith, Catriona Mclean, Brit Mollenhauer, Manuela Neumann, Kathy L. Newell, Alex Pantelyat, Manuela Pendziwiat, Annette Peters, Laura Molina Porcel, Alberto Rabano, Radoslav Matej, Alex Rajput, Ali Rajput, Regina Reimann, William K. Scott, William Seeley, Sashika Selvackadunco, Tanya Simuni, Christine Stadelmann, Per Svenningsson, Alan Thomas, Claudia Trenkwalder, Claire Troakes, John Q. Trojanowski, Ryan J. Uitti, Charles L. White, Zbigniew K. Wszolek, Tao Xie, Teresa Ximelis, Justo Yebenes, Ulrich Mueller, Gerard D. Schellenberg, Jochen Herms, Gregor Kuhlenbaumer, Gunter Hoeglinger
Summary: Multiple System Atrophy is a rare neurodegenerative disease characterized by alpha-synuclein aggregation in glial cytoplasmic inclusions. By studying autopsy-confirmed cases, it was found that rs16859966 on chromosome 3, rs7013955 on chromosome 8, and rs116607983 on chromosome 4 are the most strongly disease-associated markers.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Oleg O. Glebov, David Williamson, Dylan M. Owen, Tibor Hortobagyi, Claire Troakes, Dag Aarsland
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Neurosciences
Christina E. Toomey, Wendy E. Heywood, James R. Evans, Joanne Lachica, Sarah N. Pressey, Sandrine C. Foti, Mesfer Al Shahrani, Karishma D'Sa, Iain P. Hargreaves, Simon Heales, Michael Orford, Claire Troakes, Johannes Attems, Ellen Gelpi, Miklos Palkovits, Tammaryn Lashley, Steve M. Gentleman, Tamas Revesz, Kevin Mills, Sonia Gandhi
Summary: This study investigates the molecular drivers of early sporadic Parkinson's disease (PD) using the pathological gradient in early to mid-stage PD brains. The researchers demonstrate that mitochondrial dysfunction is detectable prior to neuronal loss and alpha-synuclein fibril deposition, suggesting that it is one of the key drivers of early disease. The study also highlights changes in brain energy metabolism and mitochondrial redox state as early events in PD.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Neurosciences
Benjamin G. Trist, Jennifer A. Fifita, Alison Hogan, Natalie Grima, Bradley Smith, Claire Troakes, Caroline Vance, Christopher Shaw, Safa Al-Sarraj, Ian P. Blair, Kay L. Double
Summary: Multiple neurotoxic proteinopathies co-exist in vulnerable neuronal populations in neurodegenerative diseases, and the interactions between these pathologies may modulate disease progression and serve as targets for disease-modifying treatments. The interactions between superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), and ubiquitin-binding protein 62/sequestosome 1 (p62) proteinopathies have been reported in animal models of amyotrophic lateral sclerosis (ALS), but have not been studied in patient tissues. In this study, the spatial relationships between SOD1, TDP-43, and p62 pathologies were explored in post-mortem spinal cord motor neurons of ALS patients, revealing co-deposition and subcellular mislocalization patterns associated with SOD1 gene status. These findings suggest that interactions between these proteins are likely to modulate the formation of their respective proteinopathies and the rate of motor neuron degeneration in ALS patients.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biology
Kornelia Szebenyi, Inigo Barrio-Hernandez, George M. Gibbons, Luca Biasetti, Claire Troakes, Pedro Beltrao, Andras Lakatos
Summary: Interrogation of amyotrophic lateral sclerosis (ALS)-linked GWAS gene networks, astrocyte-based multi-omics datasets and cellular models identifies kinesin motor protein KIF5A as a modifier of astrocyte process integrity and potential target in ALS.
COMMUNICATIONS BIOLOGY
(2023)
Article
Anatomy & Morphology
Stefano Sandrone, Marco Aiello, Carlo Cavaliere, Michel Thiebaut de Schotten, Katja Reimann, Claire Troakes, Istvan Bodi, Luis Lacerda, Serena Monti, Declan Murphy, Stefan Geyer, Marco Catani, Flavio Dell'Acqua
Summary: The histological validity of T1w/T2w myelin mapping in white matter was explored by comparing it with ex vivo postmortem histology and in vivo MRI methods (QSM and multi-echo T2 MWF mapping techniques). The results show a discrepancy between T1w/T2w myelin maps and histology, suggesting caution in using T1w/T2w as a white matter mapping method at the callosal level.
BRAIN STRUCTURE & FUNCTION
(2023)
Article
Clinical Neurology
Huzefa Rupawala, Keshvi Shah, Caitlin Davies, Jamie Rose, Marti Colom-Cadena, Xianhui Peng, Lucy Granat, Manal Aljuhani, Keiko Mizuno, Claire Troakes, Beatriz Gomez Perez-Nievas, Alan Morgan, Po-Wah So, Tibor Hortobagyi, Tara L. Spires-Jones, Wendy Noble, Karl Peter Giese
Summary: The research indicates that cysteine string protein alpha may be a more sensitive marker for early synaptic degeneration in Alzheimer's disease. Accumulations of cysteine string protein alpha are associated with beta-amyloid deposits in Alzheimer's disease and other neurodegenerative diseases.
BRAIN COMMUNICATIONS
(2022)
