Role of tau N-terminal motif in the secretion of human tau by End Binding proteins.

PLoS One

Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain, CIEN Foundation, Queen Sofia Foundation Alzheimer Center, Madrid, Spain.

Published: October 2019

For unknown reasons, humans appear to be particular susceptible to developing tau pathology leading to neurodegeneration. Transgenic mice are still undoubtedly the most popular and extensively used animal models for studying Alzheimer's disease and other tauopathies. While these murine models generally overexpress human tau in the mouse brain or specific brain regions, there are differences between endogenous mouse tau and human tau protein. Among them, a main difference between human and mouse tau is the presence of a short motif spanning residues 18 to 28 in the human tau protein that is missing in murine tau, and which could be at least partially responsible for that different susceptibility across species. Here we report novel data using affinity chromatography analysis indicating that the sequence containing human tau residues 18 to 28 acts a binding motif for End Binding proteins and that this interaction could facilitate tau secretion to the extracellular space.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342323PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210864PLOS

Publication Analysis

Top Keywords

human tau
20
tau
10
binding proteins
8
mouse tau
8
tau protein
8
human
6
role tau
4
tau n-terminal
4
n-terminal motif
4
motif secretion
4

Similar Publications

Patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) typically show abnormally high delta (<4 Hz) and low alpha (8-12 Hz) rhythms measured from resting-state eyes-closed electroencephalographic (rsEEG) activity. Here, we hypothesized that the abnormalities in rsEEG activity may be greater in ADMCI patients than in those with MCI not due to AD (noADMCI). Furthermore, they may be associated with the diagnostic cerebrospinal fluid (CSF) amyloid-tau biomarkers in ADMCI patients.

View Article and Find Full Text PDF

Advancing Alzheimer's Disease Modelling by Developing a Refined Biomimetic Brain Microenvironment for Facilitating High-Throughput Screening of Pharmacological Treatment Strategies.

Int J Mol Sci

December 2024

Department of Biochemistry, Faculty of Medicine, Level 17 Preclinical Building, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia.

Alzheimer's disease (AD) poses a significant worldwide health challenge, requiring novel approaches for improved models and treatment development. This comprehensive review emphasises the systematic development and improvement of a biomimetic brain environment to address the shortcomings of existing AD models and enhance the efficiency of screening potential drug treatments. We identify drawbacks in traditional models and emphasise the necessity for more physiologically accurate systems through an in-depth analysis of current literature.

View Article and Find Full Text PDF

Background: The potential diagnostic value of plasma amyloidogenic beta residue 42/40 ratio (Aβ42/Aβ40 ratio), neurofilament light (NfL), tau phosphorylated at threonine-181 (p-tau181), and threonine-217 (p-tau217) has been extensively discussed in the literature. We have also previously described the association between retinal biomarkers and preclinical Alzheimer's disease (AD). The goal of this study was to evaluate the association, and a multimodal model of, retinal and plasma biomarkers for detection of preclinical AD.

View Article and Find Full Text PDF

Electrophysiology-based screening identifies neuronal HtrA serine peptidase 2 (HTRA2) as a synaptic plasticity regulator participating in tauopathy.

Transl Psychiatry

January 2025

Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, and Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.

Long-term potentiation (LTP) and long-term depression (LTD) are widely used to study synaptic plasticity. However, whether proteins regulating LTP and LTD are altered in cognitive disorders and contribute to disease onset remains to be determined. Herein, we induced LTP and LTD in the hippocampal CA3-CA1 Schaffer collateral pathway, respectively, and then performed proteomic analysis of the CA1 region.

View Article and Find Full Text PDF
Article Synopsis
  • Alzheimer's disease (AD) is characterized by various pathological features including amyloid-β deposition and tau hyperphosphorylation, with cerebral microvascular dysfunction likely playing a role in its progression.
  • Researchers investigated the microvascular responses and potassium channel activity in an AD mouse model induced by streptozotocin (STZ), using behavioral tests and cellular assays.
  • The study found that STZ-AD mice showed poorer performance on behavioral tests and had impaired microvascular responses, which were further deteriorated by exposure to soluble Aβ, indicating a potential link between microvascular dysfunction and AD pathology.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!