Review
Biochemistry & Molecular Biology
Clement Barbereau, Nicolas Cubedo, Tangui Maurice, Mireille Rossel
Summary: Tauopathies encompass a diverse range of neurodegenerative diseases, with Alzheimer's disease being the most prominent one. Accumulation of abnormal forms of Tau protein in neural cells leads to its aggregation and neurofibrillary tangles, contributing to cognitive deficits and locomotor problems. Zebrafish transgenic models have been instrumental in studying Tau protein interactions and exploring neuroprotective approaches against Tau-related pathologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Lucia A. A. Giannini, Daniel T. Ohm, Annemieke J. M. Rozemuller, Laynie Dratch, EunRan Suh, Vivianna M. van Deerlin, John Q. Trojanowski, Edward B. Lee, John C. van Swieten, Murray Grossman, Harro Seelaar, David J. Irwin
Summary: FTLD-MAPT cases with different tau isoform groups show distinctive features of tau burden and neuronal degeneration, but all exhibit pronounced anterior temporal neuronal degeneration. These data suggest that genetic tauopathies with distinct isoform-related mechanisms may share similar regional vulnerability to neurodegeneration within the frontotemporal paralimbic networks.
ACTA NEUROPATHOLOGICA
(2022)
Article
Cell Biology
Abhishek Ankur Balmik, Shweta Kishor Sonawane, Subashchandrabose Chinnathambi
Summary: The study shows that HDAC6's ZnF UBP domain can modulate Tau phosphorylation, actin cytoskeleton organization, neurite extension, and ApoE nuclear localization. Additionally, it plays a role in increasing tubulin localization in the microtubule organizing center. The ZnF domain of HDAC6 is involved in various regulatory functions in neurodegenerative diseases beyond its classical role in aggresome formation.
CELL COMMUNICATION AND SIGNALING
(2021)
Review
Clinical Neurology
Bruno P. Imbimbo, Stefania Ippati, Mark Watling, Claudia Balducci
Summary: Primary tauopathies are neurological disorders characterized by tau protein deposition, while Alzheimer's disease is a secondary tauopathy. Current drugs targeting tau have not shown clinical efficacy, potentially due to clearing of physiological forms of tau. Future research focuses on developing reliable animal models and selective compounds targeting specific tau epitopes and neurotoxic tau aggregates.
ALZHEIMERS & DEMENTIA
(2022)
Article
Biochemistry & Molecular Biology
Dhiraj Acharya, Rebecca Reis, Meta Volcic, GuanQun Liu, May K. Wang, Bing Shao Chia, Rayhane Nchioua, Rudiger Gross, Jan Munch, Frank Kirchhoff, Konstantin M. J. Sparrer, Michaela U. Gack
Summary: This study reveals that actin cytoskeleton disturbance serves as a priming signal for RIG-I-like receptor (RLR)-mediated innate immunity, playing a crucial role in the defense against RNA virus infections.
Article
Geriatrics & Gerontology
Ashlyn G. Johnson, James A. Webster, Chadwick M. Hales
Summary: Using a NanoString glial profiling panel, the study investigated the alterations of glial cells in frontotemporal degeneration with tau pathology (FTD-tau). The results showed significant changes in gene expression in glial cells of FTD-tau patients compared to control samples, with increased activation of glial cell-related pathways and decreased activation of neuron-related pathways. The targeted gene panel approach provided more comprehensive gene expression information compared to proteomic analysis.
NEUROBIOLOGY OF AGING
(2022)
Article
Neurosciences
Stephanie Levert, Julie Pilliod, Etienne Aumont, Sandrine Armanville, Cyntia Tremblay, Frederic Calon, Nicole Leclerc
Summary: In this study, the interaction between Tau and FLNA proteins was explored, as well as the impact of FLNA on Tau pathology. The results showed that overexpression of FLNA led to the accumulation of Tau protein in cells, increased its phosphorylation and cleavage by Caspase-3, but did not increase its aggregation. Additionally, FLNA overexpression also induced the accumulation of annexin A2. However, in AD brains, the increase in FLNA did not correlate with Tau pathology.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Neurosciences
Maher Kurdi, Badrah Saeed Alghamdi, Jeremy Parfitt, Lee Cyn Ang
Summary: Several recent studies have described 4-repeat tauopathies characterized by globular glial inclusions, involving astrocytes or oligodendrocytes, with extensive white matter involvement and diverse neuropathological and clinical presentations. Globular glial tauopathy (GGT) is classified into three subtypes based on clinical manifestations: frontotemporal lobar degeneration, motor impairment, or a combination of both. This report presents a rare GGT case with depression and anxiety symptoms and compares its features with previously reported cases to revisit the classification.
FOLIA NEUROPATHOLOGICA
(2021)
Article
Geriatrics & Gerontology
Bora Yoon, Tengfei Guo, Karine Provost, Deniz Korman, Tyler J. Ward, Susan M. Landau, William J. Jagust
Summary: Individuals with tauopathy but without beta-amyloid show heterogeneous tau uptake patterns, indicating they may reflect more than one disorder. They share some features with Alzheimer's disease, such as cognitive impairment and neurodegeneration, but exhibit differences in characteristics such as prevalence of apolipoprotein E epsilon 4 and tau deposition patterns.
NEUROBIOLOGY OF AGING
(2022)
Article
Cell Biology
Nuria Seto-Salvia, Noemi Esteras, Rohan de Silva, Eduardo de Pablo-Fernandez, Charles Arber, Christina E. Toomey, James M. Polke, Huw R. Morris, Jonathan D. Rohrer, Andrey Y. Abramov, Rickie Patani, Selina Wray, Thomas T. Warner
Summary: The intronic mutation in the microtubule-associated protein tau gene (MAPT) increases the expression of four-repeat (4R)-tau isoforms, leading to frontotemporal lobar degeneration (FTLD). Research on astrocytes from induced pluripotent stem cells of asymptomatic carriers with the mutation showed consistently elevated levels of 4R-tau in both astrocytes and neurons. This suggests a potential involvement of astrocytes in the pathogenic process of FTLD and indicates cell-type-specific regulation that could inform treatment strategies for pre-clinical tauopathies.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Agronomy
Qi Mi, Hongqian Pang, Feishi Luan, Peng Gao, Shi Liu
Summary: The scc locus of the watermelon seed coat crack trait was fine mapped on chromosome 3, and Cla97C03G056110 was identified as the most likely candidate gene. The expression of Cla97C03G056110 was higher in non-scc lines and specifically expressed in seed coat tissue.
THEORETICAL AND APPLIED GENETICS
(2023)
Article
Cell Biology
Komaki Ninomiya, Kai Ohta, Kazunari Yamashita, Kensaku Mizuno, Kazumasa Ohashi
Summary: PLEKHG4B plays a crucial role in epithelial cell-cell junction formation by regulating actin remodeling and modulating the activities of Cdc42 and RhoA. Knockdown of PLEKHG4B leads to open junctions and aberrant myosin activity.
JOURNAL OF CELL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Hiroko Ueda, Quynh Thuy Huong Tran, Linh Nguyen Truc Tran, Koichiro Higasa, Yoshiki Ikeda, Naoyuki Kondo, Masaki Hashiyada, Chika Sato, Yoshinori Sato, Akira Ashida, Saori Nishio, Yasunori Iwata, Hiroyuki Iida, Daisuke Matsuoka, Yoshihiko Hidaka, Kenji Fukui, Suzu Itami, Norihito Kawashita, Keisuke Sugimoto, Kandai Nozu, Motoshi Hattori, Hiroyasu Tsukaguchi
Summary: Focal segmental glomerulosclerosis (FSGS) is a common kidney disease leading to end-stage renal disease. Mutations in the INF2 gene can cause monogenic FSGS or a dual-faceted disease involving peripheral neurons and podocytes. Our study compared the structural and cytoskeletal effects of different INF2 variants and found that CMT/FSGS variants caused more severe cellular defects and disrupted mitochondrial distribution and fragmentation.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Waruni C. Dissanayake, Peter R. Shepherd
Summary: This study demonstrates the importance of adherens junctions in insulin release and identifies the role of p120 catenin in regulating this process.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biology
Yanbao Xin, Guojiao Lin, Tianbao Hua, Jianmin Liang, Tianmeng Sun, Xuemei Wu
Summary: This study aimed to investigate the role of cytoskeletal proteins in epilepsy. The expression of F-actin, neurofilament proteins, and synaptophysin (SYP) was examined in a kainic acid (KA)-induced epileptic model in mice. The results showed significant decreases in F-actin and neurofilament proteins, as well as changes in SYP expression, suggesting the involvement of cytoskeletal proteins in the pathogenesis of epilepsy.
OPEN LIFE SCIENCES
(2023)
Article
Clinical Neurology
Eva Davila-Bouziguet, Arnau Casoliba-Melich, Georgina Targa-Fabra, Lorena Galera-Lopez, Andres Ozaita, Rafael Maldonado, Jesus Avila, Jose M. Delgado-Garcia, Agnes Gruart, Eduardo Soriano, Marta Pascual
Summary: Alzheimer's disease is a neurodegenerative disease characterized by the accumulation of amyloid-beta and hyperphosphorylated Tau, imbalanced neuronal activity, and cognitive deficits. A new clinical entity has been identified, which shows amyloid-beta and Tau pathologies but preserved cognition. A study using mice models found that J20/VLW mice, which accumulate amyloid-beta and hyperphosphorylated Tau, exhibit preserved hippocampal rhythmic activity and cognition, while single mutant mice show significant alterations. Furthermore, the overexpression of mutant human Tau in the hippocampal interneurons leads to a specific hyperphosphorylated Tau signature. These findings contribute to understanding the mechanisms underlying cognitive preservation in non-demented individuals with Alzheimer's disease neuropathology.
Article
Biochemistry & Molecular Biology
Laura Valles-Saiz, Rocio Peinado-Cahuchola, Jesus Avila, Felix Hernandez
Summary: Tau, a cytoskeletal protein mainly expressed in neurons, plays important roles in multiple cellular processes. This study reveals that Tau4R is the main isoform of tau expressed in the kidney, particularly in podocytes. Knockout mice without tau display a more dynamic cytoskeleton in podocytes and exhibit glomerular damage and reduced urinary creatinine.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
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)
Article
Multidisciplinary Sciences
Juan R. Perea, Esther Garcia, Laura Valles-Saiz, Raquel Cuadros, Felix Hernandez, Marta Bolos, Jesus Avila
Summary: Tauopathies are neurodegenerative diseases characterized by the accumulation of hyperphosphorylated tau protein. Inflammation, particularly the activation of microglia, is also involved in these diseases. The p38 MAPK pathway, primarily expressed in glia, has been associated with tau phosphorylation in neurodegenerative diseases like Alzheimer's Disease. Using a mouse model, researchers found increased p38 activation in microglia of the hippocampus during aging. Interestingly, these mice also displayed activated rod microglia, although p38 activation was decreased in this subpopulation. This suggests that rod microglia may have a neuroprotective phenotype in the context of tau pathology.
SCIENTIFIC REPORTS
(2022)
Article
Plant Sciences
Lizeth M. Zavala-Ocampo, Eva Aguirre-Hernandez, Perla Y. Lopez-Camacho, Rene Cardenas-Vazquez, Alejandro Dorazco-Gonzalez, Gustavo Basurto-Islas
Summary: This study reveals the acetylcholinesterase inhibition and antioxidant activity properties of P. alliacea methanol fraction and its subfractions for the first time. It establishes the basis for further research and development of new therapies for neurodegenerative disorders such as Alzheimer's disease.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Geriatrics & Gerontology
Raul Fernandez Perez, Juan Jose Alba-Linares, Juan Ramon Tejedor, Agustin Fernandez Fernandez, Miguel Calero, Aurora Roman-Dominguez, Consuelo Borras, Jose Vina, Jesus Avila, Miguel Medina, Mario Fernandez Fraga
Summary: The study reveals the presence of dementia-associated epigenetic patterns before diagnosis, highlighting the potential importance of these epigenetic alterations in the development of dementia. The findings suggest that epigenetic biomarkers based on peripheral tissues may be useful for disease detection.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Materials Science, Multidisciplinary
L. F. Gomez-Caballero, J. L. Pichardo-Molina, G. Basurto-Islas
Summary: This study reports the use of a dialysis method for simple preparation of a flexible substrate for Surface-Enhanced Raman Spectroscopy (SERS). The flexible SERS substrate showed good performance and can be used for bending surfaces in sample preparation and analysis.
Article
Neurosciences
Alvaro Sebastian-Serrano, Jesus Merchan-Rubira, Caternia Di Lauro, Carolina Bianchi, Lucia Soria-Tobar, Sonoko L. Narisawa, Jose L. Millan, Jesus Avila, Felix Hernandez, Miguel Diaz-Hernandez
Summary: This study demonstrates that increased activity of tissue-nonspecific alkaline phosphatase (TNAP) is critical for Tau-induced neurotoxicity. Upregulation of TNAP leads to intracellular Tau hyperphosphorylation and aggregation in neighboring cells, while genetic disruption of TNAP reduces the dephosphorylation of extracellular Tau, decreasing neuronal hyperactivity, brain atrophy, and hippocampal neuronal death. These findings suggest that TNAP blockade may be a novel and efficient therapy for tauopathies.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Endocrinology & Metabolism
Enrique Blazquez, Veronica Hurtado-Carneiro, Yannick LeBaut-Ayuso, Esther Velazquez, Luis Garcia-Garcia, Francisca Gomez-Oliver, Juan Miguel Ruiz-Albusac, Jesus Avila, Miguel Angel Pozo
Summary: Several neurological diseases share similar pathological alterations, including neuroinflammation and altered brain glucose metabolism. Insulin and brain glucose metabolism abnormalities are considered as key pathological substrates for these diseases and may serve as potential therapeutic targets.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Cell Biology
Daniel Ruiz-Gabarre, Almudena Carnero-Espejo, Jesus Avila, Vega Garcia-Escudero
Summary: Tau protein, encoded by the MAPT gene, has multiple physiological functions and is associated with various pathologies. The splicing of MAPT transcripts is complex, generating multiple isoforms that are spatially and developmentally regulated. These Tau isoforms play important roles in both physiology and pathology.
Review
Neurosciences
Alejandro Anton-Fernandez, Laura Valles-Saiz, Jesus Avila, Felix Hernandez
Summary: Tau protein is mainly localized in the cytoplasm of neuronal cells but can also be found in the cell nucleus, where it binds to nucleic acids. The increase in nuclear tau during aging may contribute to the activation of transposons and accelerate aging.
Article
Clinical Neurology
Rocio Alfaro-Ruiz, Carolina Aguado, Alejandro Martin-Belmonte, Ana Esther Moreno-Martinez, Jesus Merchan-Rubira, Felix Hernandez, Jesus Avila, Yugo Fukazawa, Rafael Lujan
Summary: N-methyl-D-aspartate receptors are important in Alzheimer's disease, and their expression and localization differ at synaptic and extrasynaptic sites, which is associated with accumulation of phospho-tau.
Review
Neurosciences
Natalia Molinero, Alejandro Anton-Fernandez, Falix Hernandez, Jesus Avila, Begona Bartolome, M. Victoria Moreno-Arribas
Summary: Gut microbiota is a diverse population of microorganisms in the gastrointestinal tract that influences host health and disease. Age is a conditioning factor for the vitality of the gut microbiota, and aging is a primary risk factor for neurodegenerative diseases like Alzheimer's disease (AD). This paper summarizes the emerging evidence on the link between the oral and gut microbiome and neurodegeneration, with a focus on AD.
Article
Biochemistry & Molecular Biology
Laura Valles-Saiz, Jesus avila, Felix Hernandez
Summary: The dysregulation of transposable elements is involved in neurodegenerative disorders. This study investigated the protective effects of the reverse transcriptase inhibitor lamivudine in a mouse model of Alzheimer's disease. The results showed that lamivudine treatment reduced histopathological markers of tauopathies and improved motor and cognitive functions. Additional experiments revealed that tau promotes the insertion of transposable elements, and lamivudine inhibits this insertion. These findings suggest that early administration of lamivudine may attenuate the progression of tauopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Indalo Domene-Serrano, Raquel Cuadros, Felix Hernandez, Jesus Avila, Ismael Santa-Maria
Summary: This study accurately predicted, analyzed, and understood tau protein structure and the conformational basis for the neuroprotective role of W-tau using a tridimensional deep learning-based approach and in vitro polymerization assay. The findings demonstrate the importance of the structure-function relationship on the neuroprotective behavior of W-tau inhibiting tau fibrillization in vitro.
JOURNAL OF ALZHEIMERS DISEASE REPORTS
(2023)