Untangling the Role of Tau in Physiology and Pathology

Editorial

26 May 2020

Editorial: Untangling the Role of Tau in Physiology and Pathology

Miguel Medina

and

Jesús Avila

3,501 views

6 citations

Editors

Jesus Avila

Centre for Molecular Biology Severo Ochoa, Spanish National Research Council (CSIC)

Miguel Medina

Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED)

Impact

Interpretation of astrocytic tau accumulation. 1: Astroglia expresses subtle levels of tau, which is upregulated and then hyperphosphorylated as a response to a yet unidentified neurodegeneration-inducing event. 2: Tau-overexpression and hyperphosphorylation occurs in astrocytes as a response to a non-neurodegenerative event such as blood-brain barrier dysfunction, perfusion disturbance or a local mechanical impact. 3: Internalization of pathological tau derived from synapses of projecting neurons from another brain region. 4: Internalization of pathological tau derived from local neurons.

Review

09 April 2020

Astroglia and Tau: New Perspectives

Gabor G. Kovacs

15,600 views

96 citations

Mini Review

28 January 2020

Differences Between Human and Murine Tau at the N-terminal End

Félix Hernández

, 3 more and

Jesús Avila

13,760 views

48 citations

Review

17 January 2020

Altered Levels and Isoforms of Tau and Nuclear Membrane Invaginations in Huntington’s Disease

Marta Fernández-Nogales

and

José J. Lucas

6,367 views

30 citations

Correction

18 February 2020

Corrigendum: Genetic Background Influences the Propagation of Tau Pathology in Transgenic Rodent Models of Tauopathy

Tomas Smolek

, 5 more and

Santosh Jadhav

1,979 views

0 citations

Original Research

04 December 2019

The MAPT H1 Haplotype Is a Risk Factor for Alzheimer’s Disease in APOE ε4 Non-carriers

Pascual Sánchez-Juan

, 13 more and

Agustín Ruiz

10,616 views

37 citations

Thermodynamic model of cofactor-induced aggregation and cofactor assisted seeding. Mild cofactors (e.g., polyU) form metastable complexes that do not evolve to β-sheet containing species due to a high energy barrier. This barrier can be overcome by a catalyst such as a seed. In contrast, potent cofactors (e.g., heparin) form intermediate complexes, or oligomers, that spontaneously evolved toward amyloid fibrils. In both cases, removal of the cofactors from the mature fibrils results in their depolymerization, showing that the tau-cofactor complex, and not tau only, is the building block of these fibrils.

Original Research

13 December 2019

Tau-Cofactor Complexes as Building Blocks of Tau Fibrils

Yann Fichou

, 5 more and

Songi Han

6,870 views

45 citations

Original Research

14 January 2020

Chronic PD-1 Checkpoint Blockade Does Not Affect Cognition or Promote Tau Clearance in a Tauopathy Mouse Model

Yan Lin

, 4 more and

Einar M. Sigurdsson

5,841 views

19 citations

Original Research

11 December 2019

Genetic Background Influences the Propagation of Tau Pathology in Transgenic Rodent Models of Tauopathy

Tomas Smolek

, 5 more and

Santosh Jadhav

3,609 views

9 citations

Modulation of tau protein levels during daily rhythms. (A) Representative images of immunolabeled 7 day-old male dTau-GFP fly brains with anti-PDF antibody at ZT-2 and ZT-14 (early morning and early night time-points). Scale bar is 10 μm. (B) Plot representing absolute intensity values of dTau-GFP signal in LNv somas at ZT-2 and ZT-14. Results demonstrate a significant difference between dTau fluorescent signal at the studied Zeitgeber times, with intensity values higher at ZT-2 and lower at ZT-14. (C) Plot representing dTau mRNA levels resulting from PDF neurons RNA-seq analysis (Abruzzi et al., 2017). Results demonstrate a reduction in dTau transcript levels at ZT-14 in PDF neurons when compared to dTau mRNA levels at ZT-2. Data represent mean and SEM analyzed by non-parametric Mann–Whitney statistical test (∗p < 0.05; n = 12–14 hemispheres).

Original Research

21 November 2019

Role of Tau Protein in Remodeling of Circadian Neuronal Circuits and Sleep

Mercedes Arnes

, 5 more and

Ismael Santa-Maria

6,648 views

23 citations

Glutamate stimulates the translation of tau mRNA. (A) Differentiated SH-SY5Y cells were treated with various concentrations of glutamate for 30 min, and cell extracts were examined for tau protein content by Western blotting. GAPDH served as a control. RT-PCR data of tau mRNA is also shown. (B) The signal intensity of tau protein was normalized to that of GAPDH, and expressed as a relative amount. Each value represents the mean and standard error obtained from four independent experiments. ∗P < 0.05 versus control (one-way ANOVA, followed by Tukey–Kramer post hoc test). (C) Quantitative RT-PCR of tau mRNA after exposure to various doses of glutamate concentration. (D) Differentiated SH-SY5Y cells were treated with glutamate (1 mM) for 30 min in the presence or absence of cycloheximide (20 μg/ml). Tau protein from each cell extract was analyzed by Western blotting. GAPDH was used as a loading control. (E) Levels of tau protein are expressed relative to that of GAPDH. Each value represents the mean and standard error obtained from four independent experiments. ∗∗P < 0.01 versus control or in the presence of CHX (one-way ANOVA, followed by Tukey–Kramer post hoc test).

Original Research

20 November 2019

Enhanced Tau Protein Translation by Hyper-Excitation

Shunsuke Kobayashi

, 2 more and

Akihiko Takashima

4,186 views

22 citations

Tau protein expression and tau phosphorylation in the hippocampus post-status epilepticus. (A) Illustration of intra-amygdala injection of Kainic acid (KA) in mice for the induction of status epilepticus and chronic epilepsy. Flouro-jade B (FjB) staining shows neurodegeneration in the ipsilateral hippocampus at 24 h post-KA injection. Note: absence of FjB-positive cells at 4 h post status epilepticus (n = 4 per group). FjB-positive cells are mainly localized to the ipsilateral CA3 subfield of the hippocampus. Scale bar = 200 μm. (B) Tau mRNA levels quantified by RT-qPCR showing no changes between control and post-status epilepticus (n = 4 per group). (C–E) Representative Western blot (n = 1/lane) and corresponding graphs showing an increase in total tau (Tau-1; Ctrl vs. 4 h, p = 0.03), AT8/Tau-1 (Ctrl vs. 4 h, p = 0.03; Ctrl vs. 8 h, p = 0.005) and PHF-1/Tau-1 protein levels in the ipsilateral hippocampus post-status epilepticus. GAPDH is shown as a loading control (n = 4 per group). One-way ANOVA with Fisher’s post hoc test. Data are presented as mean ± standard error of the mean (SEM). *p < 0.05, **p < 0.01, ***p < 0.001.

Original Research

12 November 2019

Tau Phosphorylation in a Mouse Model of Temporal Lobe Epilepsy

Marianna Alves

, 3 more and

Tobias Engel

5,617 views

40 citations

Tau’s amino-terminal, non-microtubule binding region exhibits a strong evolutionary increase in disorder. (A) An exemplary plot of disorder prediction by IUPred2A long is shown. Species are grouped by divergence times between their higher taxons and mammals [cyclostomes or jawless fishes—615 million years ago (MYA), cartilaginous fishes—473 MYA, bony fishes—435 MYA, coelacanths—413 MYA, amphibians—352 MYA, reptiles and birds—312 MYA and mammals as a 0 value]. R squared and p-value characterizing the linear fit to the data are presented close to each respective fitting line. (B) Average values of slopes based on linear regression analysis of predicted disorder values from all selected algorithms for full-length tau and all selected regions (NTR—green, PRR—light blue, MBR—blue and CTR—dark blue) are shown. Black dots represent values for measured slopes for the individual prediction algorithms while bars show average values. Note, that NTR and PRR show an increase in disorder, while the CTR shows a decrease. (C,D) Plots of disorder prediction by IUPred2A for NTR lacking exon 2/3 or exon 3 (C) and MBR lacking exon 10 (D) are shown. Full-length NTR and MBR as also presented in (A) are indicated by dashed lines. Species are grouped as described before. R squared and p-value characterizing the linear fit to the data are presented close to each respective fitting line.

Original Research

18 September 2019

The Evolution of Tau Phosphorylation and Interactions

Nataliya I. Trushina

, 2 more and

Roland Brandt

15,109 views

75 citations

Mini Review

04 October 2019

Role of Microglial Cells in Alzheimer’s Disease Tau Propagation

Ena Španić

, 2 more and

Goran Šimić

8,924 views

67 citations

Brief Research Report

30 August 2019

Novel Functions of the Neurodegenerative-Related Gene Tau in Cancer

Ricardo Gargini

, 1 more and

Pilar Sánchez-Gómez

6,478 views

56 citations

Original Research

10 September 2019

Restoration of Olfactory Memory in Drosophila Overexpressing Human Alzheimer’s Disease Associated Tau by Manipulation of L-Type Ca2+ Channels

James P. Higham

, 2 more and

James J. L. Hodge

7,477 views

17 citations

Brief Research Report

01 October 2019

A Novel Microtubule-Tau Association Enhancer and Neuroprotective Drug Candidate: Ac-SKIP

Yanina Ivashko-Pachima

and

Illana Gozes

3,107 views

11 citations

Assembly of tubulins into Microtubules (MTs). Models of a depolymerizing (left) and polymerized (right) MTs. The guanosine 5′ triphosphate (GTP) cap or labile domain is composed mostly of tyrosinated GTP-tubulin. The stable domain is mostly composed of detyrosinated guanosine 5′ diphosphate (GDP)-tubulin. β-tubulin subunits are represented as orange cubes in their GTP-bound states and green cubes in their GDP-bound states. α-tubulin subunits are represented as blue cubes. Red sticks planted on the cubes represent the C-terminal tail of α- and β-tubulin subunits. Tyrosination is represented by a red dot on the C-terminal tail. Two MT regions are distinguished: a labile MT region mostly composed of tyrosinated GTP-tubulins, including the GTP cap, and a stable MT region mostly consisting of assembled detyrosinated GDP-tubulins. MT depolymerization is characterized by curled protofilaments at MT ends (left).

Review

07 August 2019

Role of Tau as a Microtubule-Associated Protein: Structural and Functional Aspects

Pascale Barbier

, 7 more and

Isabelle Landrieu

68,254 views

433 citations

Calcium binding drives EFhd2 liquid-droplet formation. Human EFhd2 D105A/DH41A mutant was subjected to liquid–liquid phase separation in absence [–PEG) or presence [+PEG) of 10% Polyethylene glycol (PEG) as crowding agent plus or minus 10 mM CaCl2- The proteins were visualized by confocal microscopy. The images are representative of, at least, three independent experiments. Scale bar = 10 μm.

Original Research

13 August 2019

EFhd2 Affects Tau Liquid–Liquid Phase Separation

Irving E. Vega

, 1 more and

Nicholas M. Kanaan

6,987 views

31 citations

CST aggregates are reduced by PD-901 and D-JNKI-1 treatment in SH-SY5Y cells. (A) WB and corresponding quantification of phosphorylated epitopes S202/T205, S231, S356 in CST reporter cells treated with PD-901 or D-JNKI-1 (N = 4). (B) FRET measured by sensitized emission in reporter cells treated with PD-901 or D-JNKI-1. CFP (cyan), YFP (yellow) and Normalized FRET (NFRET) images (false color). White scale bar = 10 μm. (C) Box plot of iNFRET values calculated in CST reporter cells treated with seeds (CTR) (N = 37), seeds and PD-901 treated cells (N = 27), seeds and D-JNKI-1 treated cells (N = 20). Box spans the standard error of the mean while whiskers indicates the standard deviation (∗∗∗p < 0.001 ANOVA one-way test).

Original Research

21 August 2019

Identification of an ERK Inhibitor as a Therapeutic Drug Against Tau Aggregation in a New Cell-Based Assay

Giacomo Siano

, 7 more and

Cristina Di Primio

5,197 views

24 citations

Fetching...

Open for submission

Frontiers in Cellular Neuroscience

Perinatal Programming of Brain and Behavior by Early Life Adversity: from Bench to Bedside

Edited by Harmen J Krugers, Angela Sarabdjitsingh

77.7K

views

authors

articles

Frontiers in Cellular Neuroscience

Perinatal Programming of Brain and Behavior by Early Life Adversity: from Bench to Bedside

Edited by Harmen J Krugers, Angela Sarabdjitsingh

77.7K

views

authors

articles

Frontiers in Psychiatry

Edited by Hsien-Yuan Lane, Chieh-Hsin Lin, Kenji Hashimoto

199.7K

views

authors

articles

Frontiers in Psychiatry

Integrating Molecular Research into Clinical Psychiatry: an Application to Schizophrenia and Mood Disorders

Edited by Tetsufumi Kanazawa, Hiroyuki Toda, Shuken Boku, Ryouhei Ishii

31.3K

views

authors

articles

Frontiers in Psychiatry

Neuroimaging and Genetic Biomarkers to Explore Differences between Unipolar Depression and Bipolar Disorder

Edited by Haojuan Tao, Shuixia Guo, Hengyi Cao, Ling Qin Wei, Wenhui Yang

18K

views

authors

articles

Frontiers in Psychiatry

Bridging Neuro-Immune System and Gut Microbiota in Neuropsychiatric Disorders

Edited by Mingbang Wang, Shaohua Hu, Jijun Li, Chuntao Zhao, Peng Zhong

17.6K

views

authors

articles