Review
Cell Biology
Majedul Islam, Fengyun Shen, Deepika Regmi, Katherine Petersen, Md Raza Ul Karim, Deguo Du
Summary: Abnormal tau deposition is a key characteristic of Alzheimer's disease and other neurodegenerative disorders. Recent studies have focused on the formation of tau droplets through liquid-liquid phase separation (LLPS), which have been found to promote and stabilize microtubule assembly. It is hypothesized that the progression from phase-separated tau droplets to gel-like structures and eventually fibrils is associated with the pathology of neurodegenerative diseases.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alisa Cario, Christopher L. Berger
Summary: The etiology of Tauopathies is usually explained by Tau dysfunction leading to loss of axonal microtubule stability. However, Tau has multiple functions beyond regulating microtubule dynamics, including modulating motor proteins, acting as a signaling hub, and serving as a scaffolding protein. Due to the dynamic nature of Tau isoform expression, post-translational modifications, and conformational flexibility, there is no single mechanism to describe Tau dysfunction. Studying the effects of specific pathogenic mutations or aberrant modifications on all of Tau's functions is essential to understand the unique etiology of each disease state.
Article
Neurosciences
Ryan A. Cloyd, John Koren, Jose F. Abisambra, Bret N. Smith
Summary: Our study revealed that both tau(-/-) and htau mice exhibited reduced neuronal excitability compared to age-matched controls, indicating that functional tau absence has a stronger impact on neuronal excitability than the presence of pathologic tau. These findings suggest a more complex relationship between tau pathology and neuronal excitability than previously thought.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Clinical Neurology
Ruben Smith, Nicholas C. Cullen, Alexa Pichet Binette, Antoine Leuzy, Kaj Blennow, Henrik Zetterberg, Gregory Klein, Edilio Borroni, Rik Ossenkoppele, Shorena Janelidze, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Erik Stomrud, Oskar Hansson
Summary: Baseline tau-PET and a composite baseline cognitive score were the strongest independent predictors of cognitive decline in patients with amnestic MCI or mild dementia.
ALZHEIMERS & DEMENTIA
(2022)
Article
Neurosciences
Kayo Yukawa, Satomi Yamamoto-Mcguire, Louis Cafaro, Christine Hong, Fredrik Kamme, Tsuneya Ikezu, Seiko Ikezu
Summary: TTBK1 is an attractive therapeutic target in the early stages of AD, as it can delay the progression of tau pathology by suppressing the expression of phosphorylated tau.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Geriatrics & Gerontology
Henika Patel, Pablo Martinez, Abigail Perkins, Xavier Taylor, Nur Jury, David McKinzie, Cristian A. Lasagna-Reeves
Summary: Pathological aggregation of tau and neuroinflammatory changes are crucial in the clinical course of Alzheimer's disease and related tauopathies. The PS19 mouse model study suggests that different pathological tau species may be associated with different functional deficits, and neuroinflammation may contribute to functional deficits independently of tau pathology.
NEUROBIOLOGY OF AGING
(2022)
Review
Immunology
Nastaran Karimi, Feyza Bayram Catak, Ebru Arslan, Amene Saghazadeh, Nima Rezaei
Summary: Tau, a protein associated with more than 25 neurological disorders, has been the target of research for finding novel therapeutic agents. This article reviews the latest animal and clinical studies on tau-based immunotherapies and drugs for Alzheimer's disease and progressive supranuclear palsy.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Neurosciences
Dah-eun Chloe Chung, Shanu Roemer, Leonard Petrucelli, Dennis W. Dickson
Summary: Pathological tau can promote aggregation and propagation of endogenous tau, but tauopathies differ in terms of predominant tau isoforms and selective vulnerability of brain regions. Variability in tau pathology in neuronal and glial cells challenges our understanding of tauopathies and the development of therapeutic strategies.
MOLECULAR NEURODEGENERATION
(2021)
Article
Neurosciences
Nicholas M. Kanaan, Tessa Grabinski
Summary: Tau is a versatile protein found in various cell types in the adult CNS, including neurons and mature oligodendrocytes. Different antibodies used for labeling tau show varied results, indicating the complexity of tau distribution and the need for careful interpretation of experimental data. The findings provide insights into the normal distribution of tau and its role in different compartments within the brain under both physiological and diseased conditions.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Dianne Marquez Lopez, Connor J. Maltby, Hannah Warming, Nullin Divecha, Mariana Vargas-Caballero, Mark J. Coldwell, Katrin Deinhardt
Summary: In Alzheimer's disease, tau pathology is spread through neuronal networks via a prion-like mechanism. The secretion of tau protein, both healthy and pathological, remains not fully understood. This study found that both wild-type and mutant tau were secreted in basal conditions, with mutant tau being more robustly secreted. Pharmacological stimulation of neuronal activity increased tau secretion, while inhibition of activity had no effect. Heparin sulfate proteoglycans (HSPGs) were found to play a crucial role in the secretion of tau, regardless of activity dependence.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Pharmacology & Pharmacy
Majedul Islam, Fengyun Shen, Deepika Regmi, Deguo Du
Summary: Tauopathies are neurodegenerative diseases characterized by abnormal tau deposition in the brain. Currently, there are no approved disease-modifying therapies for tauopathies. Drug repurposing offers a potential alternative approach to discover effective drugs for treating these diseases.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Cell Biology
Xiaohuan Sun, Victor C. Ogbolu, Peter W. Baas, Liang Qiang
Summary: Tau, one of the most abundant microtubule-associated protein, plays a role in regulating microtubule dynamics and shaping the morphology of axons in neurons. Recent studies challenge the traditional view of tau as a microtubule stabilizer and shed light on its complex role in regulating various properties of microtubules. While reducing tau levels shows promise for early tauopathies, efficacy decreases in later stages due to toxic tau aggregates and neurofibrillary tangles. The interplay between tau and MAP6, another microtubule-associated protein, adds complexity to tau's regulation of microtubule dynamics. Maintaining a delicate balance between these proteins is crucial for neuronal function. Therefore, tau reduction therapies require a comprehensive understanding of disease progression, considering functional tau loss, toxic aggregates, and microtubule dynamics. Stage-dependent application and potential unintended consequences must be carefully evaluated. Restoring microtubule dynamics in late-stage tauopathies may require alternative strategies.
Review
Biochemistry & Molecular Biology
Naruhiko Sahara, Makoto Higuchi
Summary: Tauopathies are neurodegenerative diseases characterized by the accumulation of fibrillar tau in neurons and glial cells. While their association with cognitive deficits is well-known, the causal mechanisms underlying tau-induced neuronal dysfunction are still not fully understood. Recent advancements have allowed for the classification of tauopathies based on the core structures of tau filaments. In vivo visualization of tau pathology is now possible using specific positron emission tomography tracers. Therapeutic strategies include selective degradation of pathological tau species and enhancing the clearance of tau through neuron-glia networks. Additionally, the development of neuroinflammatory biomarkers is necessary to understand the contribution of immune cells in preventing neurodegeneration.
Article
Neurosciences
Solene Ferreira, Kimberley A. Pitman, Benjamin S. Summers, Shiwei Wang, Kaylene M. Young, Carlie L. Cullen
Summary: The study found that MAPT(P301S) transgenic mice experience significant turnover of oligodendrocytes, with newborn oligodendrocytes compensating for myelin loss early in the development of tauopathy.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Clinical Neurology
Annika van Hummel, Goce Taleski, Jean-Marie Sontag, Astrid Feentje Feiten, Yazi D. Ke, Lars M. Ittner, Estelle Sontag
Summary: In this study, it was found that dietary supplementation with L-methylfolate, choline, and betaine can reduce phosphorylation of tau protein and associated behavioral phenotypes in the TAU58/2 mouse model. These findings provide experimental evidence that boosting one-carbon metabolism may be a potential therapeutic strategy for tauopathies.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
