Review
Immunology
Yijun Chen, Yang Yu
Summary: Alzheimer's Disease (AD) is mostly responsible for dementia, characterized by neuritic plaques and neurofibrillary tangles containing aggregated β-amyloid (Aβ) and hyperphosphorylated tau protein. Recent focus has been on disease-modifying therapy targeting Aβ, although the efficacy and long-term safety of such drugs are still controversial. Tau has gained attention as a therapeutic target due to its association with cognitive dysfunction. Inflammation, especially neuroinflammation, is linked to AD and tau pathology. Understanding the relationship between tau pathology and neuroinflammation will contribute to discovering therapeutic targets for AD and other tau-related diseases.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Cell Biology
M. Bell-Simons, S. Buchholz, J. Klimek, H. Zempel
Summary: This study used a laser-based axotomy model combined with confocal microscopy to investigate the distribution of Tau protein in axons and its relationship with protein transport. The results suggest that axonal damage does not lead to the accumulation of Tau protein in the cell body or an increase in AT8 Tau phosphorylation.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Frederique Hart J. de Ruyter, Tjado H. J. Morrema, Jurre den Haan, Jos W. R. Twisk, Johannes F. de Boer, Philip Scheltens, Baayla D. C. Boon, Dietmar R. Thal, Annemieke J. Rozemuller, Frank D. Verbraak, Femke H. Bouwman, Jeroen J. M. Hoozemans, Netherlands Brain Bank
Summary: This study assessed the presence of p-tau in the retina in relation to tau pathology in the brain. The findings suggest that retinal p-tau could serve as potential biomarkers for Alzheimer's disease and primary tauopathies.
ACTA NEUROPATHOLOGICA
(2022)
Article
Clinical Neurology
Chihiro Sato, Nipun Mallipeddi, Nupur Ghoshal, Brenton A. Wright, Gregory S. Day, Albert A. Davis, Albert H. Kim, Gregory J. Zipfel, Randall J. Bateman, Audrey Gabelle, Nicolas R. Barthelemy
Summary: High pT217/T217 and low Aβ42/40 were found in CSF of AD patients, while low pT217/T217 and normal Aβ42/40 were observed in 3R+4R tauopathies patients and cognitively normal individuals. The CSF pT217/T217 x CSF Aβ42/40 composite biomarker is sensitive in distinguishing MAPT R406W carriers from other groups.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Cell Biology
Katelyn Mroczek, Sanjanie Fernando, Paul R. Fisher, Sarah J. Annesley
Summary: Tau and alpha-synuclein exhibit different but overlapping patterns of intracellular localization, exerting distinct but overlapping patterns of cytotoxic effects. They may interact physically in the cell cortex, affecting some phenotypes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jakub Sinsky, Karoline Pichlerova, Jozef Hanes
Summary: Tau protein is crucial for the normal function of neurons and the brain by regulating microtubules, but in diseased conditions, pathological modifications can lead to aggregation and formation of harmful structures like PHFs and NFTs, causing neuronal loss and death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Luca Pinzi, Nicolo Bisi, Claudia Sorbi, Silvia Franchini, Nicolo Tonali, Giulio Rastelli
Summary: Tau is a protein with large structural portions that undergo extended conformational changes. Accumulation of Tau protein into toxic aggregates in neuronal cells leads to severe tauopathies. Recent research advancements have provided a better understanding of Tau structures and their implications in different tauopathies. This review presents an up-to-date overview of Tau structures reported in the Protein Data Bank, focusing on the connections between structural features, tauopathies, crystallization conditions, and sample types. The information presented highlights interesting links that could aid in the design of compounds to modulate Tau aggregation.
Article
Neurosciences
Zuha Waheed, Jawaria Choudhary, Faria Hasan Jatala, Aneeqa Noor, Inga Zerr, Saima Zafar
Summary: Tau is a microtubule-associated binding protein in the nervous system that stabilizes microtubules in nerve cells. It accumulates as aggregates and tangles, leading to various pathologies. Different splice variants of tau are expressed in the brain and contribute to neurodegenerative diseases. The isoforms have different roles and undergo post-translational modifications at different rates, affecting their physiological and pathological attributes. This article aims to review the roles of tau isoforms and their underlying mechanisms in neurological deficits.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Yuying Li, Tianqing Liu, Mengchao Cui
Summary: This review summarizes the latest development of Tau tracers and analyzes their chemical structures and biological properties. The limitations of current tracers and considerations for the development of new tracers are also discussed.
CHINESE CHEMICAL LETTERS
(2022)
Article
Medicine, Research & Experimental
Weijin Wang, Qiuzhi Zhou, Tao Jiang, Shihong Li, Jinwang Ye, Jie Zheng, Xin Wang, Yanchao Liu, Minmin Deng, Dan Ke, Qun Wang, Yipeng Wang, Jian-Zhi Wang
Summary: The novel small-molecule PROTAC, C004019, showed promising results in selectively promoting tau protein clearance and improving synaptic and cognitive functions.
Article
Biochemistry & Molecular Biology
Narendran Annadurai, Jiri Hruby, Agata Kubickova, Lukas Malina, Marian Hajduch, Viswanath Das
Summary: Tauopathies are neurodegenerative diseases categorized into three types based on tau isoforms. Differences in seeding propensities and induction of tau aggregation were observed between R2 and R3 aggregates. The accumulation of pSer262 tau was visible earlier in cells induced with R2 aggregates, suggesting a role for the R2 region in disease progression and neuropathology of 4R tauopathies.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Neurosciences
Juan R. Perea, Marta Bolos, Raquel Cuadros, Esther Garcia, Vega Garcia-Escudero, Felix Hernandez, Roisin M. McManus, Michael T. Heneka, Jesus Avila
Summary: This study demonstrates that inhibiting p38 can attenuate the toxic effect of tau in microglia and enhance microglia-mediated tau phagocytosis.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Clinical Neurology
Antoine Duquette, Camille Pernegre, Ariane Veilleux Carpentier, Nicole Leclerc
Summary: Tau protein becomes hyperphosphorylated in tauopathies, leading to its redistribution from axon to soma-dendrites. The pattern of hyperphosphorylation varies in different regions of the brain in each tauopathy, affecting both neurons and glial cells. Hyperphosphorylated tau is also observed in physiological conditions, such as hibernation and brain development.
FRONTIERS IN NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hannah Ennerfelt, Elizabeth L. Frost, Daniel A. Shapiro, Coco Holliday, Kristine E. Zengeler, Gabrielle Voithofer, Ashley C. Bolte, Catherine R. Lammert, Joshua A. Kulas, Tyler K. Ulland, John R. Lukens
Summary: Recent studies have highlighted the critical roles of microglia and their receptors in controlling neurotoxic material in neurodegenerative diseases. SYK plays an important role in neuroprotective functions of microglia, with its deletion exacerbating AD deposition and neuropathology. In addition, SYK regulates microglial phagocytosis and DAM acquisition in demyelinating disease.
Article
Chemistry, Multidisciplinary
Rinie Bajracharya, Esteban Cruz, Jurgen Gotz, Rebecca M. Nisbet
Summary: Tau-specific immunotherapy is a promising treatment strategy for Alzheimer's disease. However, the blood-brain barrier poses a challenge for effective delivery of tau-specific antibodies. Previous research has shown that low-intensity scanning ultrasound combined with microbubbles can increase antibody passage into the brain. This study aimed to assess the therapeutic response of ultrasound-mediated delivery of tau-specific antibodies.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Clinical Neurology
Khayrun Nahar, Thibaud Lebouvier, Maarja Andaloussi Mae, Anne Konzer, Jonas Bergquist, Yvette Zarb, Bengt Johansson, Christer Betsholtz, Michael Vanlandewijck
Article
Biochemistry & Molecular Biology
Alice Prigent, Guillaume Chapelet, Adrien De Guilliem de Lataillade, Thibauld Outlier, Emilie Durieu, Arnaud Bourreille, Emilie Duchalais, Kevin Hardonniere, Michel Neunlist, Wendy Noble, Saadia Kercline-Romer, Pascal Derkinderen, Malvyne Rolli-Derkinderen
Review
Pharmacology & Pharmacy
Israel Olapeju Bolanle, Kirsten Riches-Suman, Ritchie Williamson, Timothy M. Palmer
Summary: Protein O-GlcNAcylation has emerged as a new mechanism in the pathogenesis of cardiovascular diseases, playing a vital role in modulating vascular homeostasis and cardiac function through altering cellular functions of target proteins. Studying this mechanism may provide new therapeutic targets for the development of more effective medicines.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Cell Biology
Dan Wu, Sailan Wang, Daniel V. Oliveira, Francesca Del Gaudio, Michael Vanlandewijck, Thibaud Lebouvier, Christer Betsholtz, Jian Zhao, ShaoBo Jin, Urban Lendahl, Helena Karlstrom
Summary: Infantile myofibromatosis (IMF) is a benign tumor characterized by nonmetastatic tumors, with some cases associated with NOTCH3 gene mutations. Specifically, the NOTCH3L1519P mutation leads to enhanced downstream signaling but absence from the cell surface, instead accumulating in the endoplasmic reticulum. Treatment with chloroquine reduces secreted mutated extracellular domain and decreases signaling, while NOTCH3L1519P also upregulates PDGFRB expression in fibroblasts.
DISEASE MODELS & MECHANISMS
(2021)
Review
Biochemistry & Molecular Biology
Pascal Derkinderen, Malvyne Rolli-Derkinderen, Guillaume Chapelet, Michel Neunlist, Wendy Noble
Summary: The enteric nervous system, often referred to as the 'second brain', shares many features with the central nervous system and may be susceptible to neurodegenerative diseases similar to those affecting the brain. Current studies focus on the expression and phosphorylation pattern of tau protein in the enteric nervous system, exploring the potential occurrence of 'enteric tauopathies'.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Cardiac & Cardiovascular Systems
Israel O. Bolanle, Kirsten Riches-Suman, Mahmoud Loubani, Ritchie Williamson, Timothy M. Palmer
Summary: Coronary artery bypass graft (CABG) using autologous saphenous vein remains the gold standard for treating CAD patients, but those with T2DM are at higher risk of graft failure. Protein O-GlcNAcylation has emerged as a key mechanism in the pathogenesis of vein graft failure in T2DM, providing potential therapeutic targets for new drug development.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Erica Staurenghi, Valentina Cerrato, Paola Gamba, Gabriella Testa, Serena Giannelli, Valerio Leoni, Claudio Caccia, Annalisa Buffo, Wendy Noble, Beatriz Gomez Perez-Nievas, Gabriella Leonarduzzi
Summary: Among the brain hallmarks of Alzheimer's disease, reactive astrocytes are correlated with neuronal loss and cognitive deficits, while alterations in brain cholesterol metabolism contribute to AD pathogenesis. Oxysterols in AD brains induce astrocyte reactivity and the release of mediators that impact neuronal health and synapses, with lipocalin-2 playing a key role in mediating the synaptotoxic effect of oxysterol-treated astrocytes.
Article
Cell Biology
Patricia Gomez-Suaga, Gabor M. Morotz, Andrea Markovinovic, Sandra M. Martin-Guerrero, Elisavet Preza, Natalia Arias, Keith Mayl, Afra Aabdien, Vesela Gesheva, Agnes Nishimura, Ambra Annibali, Younbok Lee, Jacqueline C. Mitchell, Selina Wray, Christopher Shaw, Wendy Noble, Christopher C. J. Miller
Summary: This study reveals that hexanucieotide repeat expansions in C9orf72 disrupt the ER-mitochondria signalling and VAPB-PTPIP51 tethers, leading to neurotoxicity. The interaction between VAPB-PTPIP51 is disrupted by neurotoxic DPRs, potentially involving the activation of GSK3β. Furthermore, these DPRs also disrupt the delivery of Ca2+ from ER stores to mitochondria, which is a primary function of the VAPB-PTPIP51 tethers. These findings identify a new molecular target for mutant C9orf72-mediated toxicity.
Article
Immunology
Beatriz G. Perez-Nievas, Louisa Johnson, Paula Beltran-Lobo, Martina M. Hughes, Luciana Gammallieri, Francesca Tarsitano, Monika A. Myszczynska, Irina Vazquez-Villasenor, Maria Jimenez-Sanchez, Claire Troakes, Stephen B. Wharton, Laura Ferraiuolo, Wendy Noble
Summary: The pathological interactions between beta-amyloid (A beta) and tau contribute to synapse loss and cognitive decline in Alzheimer's disease (AD). Reactive astrocytes play a prominent role in AD brain and exacerbate the synaptotoxic effects of A beta through the interaction of astrocytic CXCL1 and neuronal CXCR2 receptors, suggesting a potential novel therapeutic target.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Biochemistry & Molecular Biology
Chen Lyu, Stefano Da Vela, Youssra Al-Hilaly, Karen E. Marshall, Richard Thorogate, Dmitri Svergun, Louise C. Serpell, Annalisa Pastore, Diane P. Hanger
Summary: Tau35 is a truncated form of tau found in human brain in certain tauopathies, and its expression in mice recapitulates key features of human disease including increased tau phosphorylation and cognitive/motor dysfunction. Structural characterization revealed that Tau35 exhibits higher rigidity and a higher propensity to aggregate compared to longer tau isoforms 2N3R and 2N4R. Tau35 aggregates are morphologically similar to previously reported tau fibrils but more densely packed, shedding light on their potentially damaging role in tauopathies.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Clinical Neurology
Florent El Grabli, Francois Quesque, Celine Borg, Michael Witthoeft, George A. Michael, Christian Lucas, Florence Pasquier, Thibaud Lebouvier, Maxime Bertoux
Summary: This study found that patients with chronic low back pain have lower interoceptive accuracy and mentalizing abilities, but there was no correlation between these performances.
Article
Clinical Neurology
Julien Dumurgier, Severine Sabia, Henrik Zetterberg, Charlotte E. Teunissen, Bernard Hanseeuw, Adelina Orellana, Susanna Schraen, Audrey Gabelle, Merce Boada, Thibaud Lebouvier, Eline A. J. Willemse, Emmanuel Cognat, Agustin Ruiz, Claire Hourregue, Matthieu Lilamand, Elodie Bouaziz-Amar, Jean-Louis Laplanche, Sylvain Lehmann, Florence Pasquier, Philip Scheltens, Kaj Blennow, Archana Singh-Manoux, Claire Paquet
Summary: This study proposes a new algorithm to establish cutoffs for CSF biomarkers of Alzheimer's disease (AD) and validates it against CSF classification derived from PET imaging. The algorithm shows high agreement with the PET imaging-based classification and can potentially reduce heterogeneity in AD classification.
Article
Clinical Neurology
Cindy C. C. Pang, Maja H. Sorensen, Krit Lee, Kelvin C. Luk, John Q. Trojanowski, Virginia M. Y. Lee, Wendy Noble, Raymond C. C. Chang
Summary: This study investigates the role of pathological alpha-synuclein in Parkinson's disease. The results suggest that spread/replication of pathological aSyn may not be sufficient to induce neurodegenerative changes. Instead, oxidative stress responses and aSyn accumulation are associated with other Parkinson's disease-associated abnormalities and cognitive dysfunction.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Paula Beltran-Lobo, Matthew J. Reid, Maria Jimenez-Sanchez, Alexei Verkhratsky, Beatriz G. Perez-Nievas, Wendy Noble
Summary: Astrocytes play important roles in maintaining the balance and defense of the central nervous system. In Alzheimer's disease, astrocytes undergo various changes and are closely associated with abnormal protein aggregates. This review focuses on the P2X7 receptor and its contribution to altered astrocyte functions in Alzheimer's disease. Animal studies have shown that targeting P2X7 receptor can improve cognitive and synaptic impairments in models of the disease.
ESSAYS IN BIOCHEMISTRY
(2023)
Review
Clinical Neurology
Sarah J. Marzi, Brian M. Schilder, Alexi Nott, Carlo Sala Frigerio, Sandrine Willaime-Morawek, Magda Bucholc, Diane P. Hanger, Charlotte James, Patrick A. Lewis, Ilianna Lourida, Wendy Noble, Francisco Rodriguez-Algarra, Jalil-Ahmad Sharif, Maria Tsalenchuk, Laura M. Winchester, Umran Yaman, Zhi Yao, Janice M. Ranson, David J. Llewellyn
Summary: This article reviews the application of artificial intelligence (AI) and machine learning (ML) in dementia research. The challenges of reproducibility and cross-species translation are discussed, and the potential of AI and ML methods to enhance research and translation is evaluated. Data resources and AI approaches are highlighted as solutions, and the exciting future possibilities of multi-omics analysis with AI in drug discovery are mentioned.
ALZHEIMERS & DEMENTIA
(2023)