Review
Biochemistry & Molecular Biology
Raquel Sanchez-Varo, Marina Mejias-Ortega, Juan Jose Fernandez-Valenzuela, Cristina Nunez-Diaz, Laura Caceres-Palomo, Laura Vegas-Gomez, Elisabeth Sanchez-Mejias, Laura Trujillo-Estrada, Juan Antonio Garcia-Leon, Ines Moreno-Gonzalez, Marisa Vizuete, Javier Vitorica, David Baglietto-Vargas, Antonia Gutierrez
Summary: This review provides an overview of the major pathological elements of Alzheimer's disease and discusses the insights provided by mouse models in understanding the underlying mechanisms. It highlights the pros and cons of current models and explores the potential benefits of combining transgenic mice with omics technologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Naruhiko Sahara, Rin Yanai
Summary: Neurofibrillary tangles composed of hyperphosphorylated tau protein are key features of tauopathy. However, there is a limited number of animal models that display intracellular tau pathology. Recent studies have shown that transgenic mice expressing mutant tau successfully develop neurofibrillary pathology, but there are limitations and pitfalls to be addressed.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Aiko Robert, Michael Scholl, Thomas Vogels
Summary: Recent research has shown that injecting purified tau aggregates from human tauopathy patients can replicate the structural features and cell type specificity of the original tau pathology. These models may have unique translational value in studying the functional consequences of tau pathology, tau-based diagnostics, and tau-targeting therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Rahul Kumar, Vishvanath Tiwari, Sharmistha Dey
Summary: This article discusses the role of Pyk2 in the pathogenesis of Alzheimer's disease and its potential as a therapeutic drug.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Review
Neurosciences
Paulino Ramirez, Gabrielle Zuniga, Wenyan Sun, Adrian Beckmann, Elizabeth Ochoa, Sarah L. DeVos, Bradley Hyman, Gabriel Chiu, Ethan R. Roy, Wei Cao, Miranda Orr, Virginie Buggia-Prevot, William J. Ray, Bess Frost
Summary: The study reveals that transposable elements are activated in the context of brain aging and tauopathy in mice, with endogenous retrovirus (ERV) class of retrotransposons being particularly enriched. Protein encoded by Intracisternal A-particle is found to be elevated in tau transgenic mouse brains. The research also suggests increased DNA copy number of transposable elements in the brains of tau transgenic mice, indicating potential retrotransposition activity in the context of tauopathy.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Chemistry, Analytical
Li-En Lin, Kun Miao, Chenxi Qian, Lu Wei
Summary: Amyloid aggregation, a pathological hallmark in neurodegenerative diseases, was studied using label-free high-resolution imaging and machine learning for specific segmentation of aggregate cores and peripheral filaments. This non-invasive imaging technology allows precise and multiplex high-resolution imaging of protein aggregates and their micro-environment, opening up new biomedical applications.
Article
Medicine, Research & Experimental
Ha-Lim Song, Na-Young Kim, Jaewan Park, Meong Il Kim, Yu-Na Jeon, Se-Jong Lee, Kwangmin Cho, Young-Lim Shim, Kyoung-Hye Lee, Yeon-Seon Mun, Jung-A Song, Min-Seok Kim, Chan-Gi Pack, Minkyo Jung, Hyemin Jang, Duk L. Na, Minsun Hong, Dong-Hou Kim, Seung-Yong Yoon
Summary: This study identifies acetylated K280 as a key tau species involved in propagation, and the developed Y01 antibody specifically target acetylated K280. Y01 can prevent tauopathy progression by neutralizing and phagocytizing acetylated tau aggregates, making it a promising therapeutic candidate for Alzheimer's disease and other tauopathies.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Multidisciplinary Sciences
Aamir S. Mukadam, Lauren V. C. Miller, Annabel E. Smith, Marina Vaysburd, Siri A. Sakya, Sophie Sanford, Sophie Keeling, Benjamin J. Tuck, Taxiarchis Katsinelos, Chris Green, Lise Skov, Sanne S. Kaalund, Stian Foss, Keith Mayes, Kevin 'Connell, Mark Wing, Claire Knox, Jessica Banbury, Edward Avezov, James B. Rowe, Michel Goedert, Jan Terje Andersen, Leo C. James, William A. McEwan
Summary: Passively transferred antibodies can target and protect against tau pathology in neurodegenerative diseases. The cytosolic Ab receptor and E3 ligase TRIM21 have been identified as potential mechanisms of antibody protection against tau aggregation.
Article
Multidisciplinary Sciences
Randall J. Eck, Rebecca L. Kow, Aristide H. Black, Nicole F. Liachko, Brian C. Kraemer
Summary: The pathological accumulation of the microtubule binding protein tau is the main cause of age-related neurodegenerative diseases known as tauopathies. A study using a Caenorhabditis elegans model found that the toxicity of tau depends on the nuclear E3 ubiquitin ligase adaptor protein SPOP. Loss of function mutations in the spop-1 gene improved behavioral deficits in tau transgenic animals, while overexpression of SPOP-1 worsened these deficits. Furthermore, loss of spop-1 rescued various tau-related phenotypes, including tau protein accumulation, neurodegeneration, and shortened lifespan.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Neurosciences
Hironori Takamura, Yoshiaki Nakayama, Hidefumi Ito, Taiichi Katayama, Paul E. Fraser, Shinsuke Matsuzaki
Summary: The study suggests that SUMO1 conjugation with tau protein in progressive supranuclear palsy (PSP) promotes aggregation and impedes removal of protein deposits. The fusion of truncated tau with SUMO1 leads to increased oligomerization and accumulation on microtubules, while SUMO2 fusion protein does not show significant alteration in cytoplasmic distribution or tau aggregation. Blocking proteasome-mediated degradation enhances aggregation of tau-SUMO1 fusion protein, indicating that SUMO1 modification of truncated tau may contribute to PSP pathogenesis.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Neurosciences
Arpita Bera, Gantyada Lavanya, Ravada Reshmi, Kapil Dev, Rahul Kumar
Summary: This article discusses the role of Drp1 in the pathogenesis of Alzheimer's disease and the potential of Drp1 inhibitors as therapeutic drugs for AD in the future.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
M-A de Fisenne, Z. Yilmaz, R. De Decker, V Suain, L. Buee, K. Ando, J-P Brion, K. Leroy
Summary: Research suggests that there is a low risk of tau pathology transmission during eye surgery using AD tissue material, and that retinal ganglion cells exhibit a resistance to develop a tau pathology.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Clinical Neurology
Sarah Houben, Megane Homa, Zehra Yilmaz, Karelle Leroy, Jean-Pierre Brion, Kunie Ando
Summary: AHN plays a critical role in sustaining hippocampal functions such as learning and memory, and impaired AHN in AD patients may contribute to cognitive deficits. NFTs and amyloid plaques are key neuropathological hallmarks of AD, with abnormal tau protein accumulation impacting AHN. Further research is needed to fully understand the relationship between tau pathology and AHN.
FRONTIERS IN NEUROLOGY
(2021)
Article
Cell Biology
Francheska Delgado-Peraza, Carlos J. Nogueras-Ortiz, Olga Volpert, Dong Liu, Edward J. Goetzl, Mark P. Mattson, Nigel H. Greig, Erez Eitan, Dimitrios Kapogiannis
Summary: The study found that biomarkers in circulating NEVs and AEVs reflect their brain levels across multiple AD mouse models, supporting their potential use as a liquid biopsy for neurological disorders. This demonstrates a potential for utilizing EV proteins as AD biomarkers and emphasizes the importance of further research in this area.
Review
Neurosciences
Preetpal Kaur, Alisha Khera, Hema K. Alajangi, Akanksha Sharma, Pradeep K. Jaiswal, Gurpal Singh, Ravi P. Barnwal
Summary: Several protein kinases and phosphatases regulate tau protein phosphorylation, and an imbalance in their activity leads to tau hyper-phosphorylation. Aberrant tau phosphorylation causes it to dissociate from microtubules and form neurofibrillary tangles, contributing to neurodegenerative disorders. Restorative approaches targeting hyperphosphorylated tau protein are being explored, and drug delivery systems based on nanocarriers provide a potential solution for the limited transport of drugs to the central nervous system. This review discusses tau protein, regulation of its phosphorylation, drugs in use or under clinical trials, and treatment strategies for tauopathies based on the role of tau hyperphosphorylation in disease pathogenesis.
MOLECULAR NEUROBIOLOGY
(2023)