Immunological demonstration of tau protein in neurofibrillary tangles

2006 ◽  
pp. 307-312
Author(s):  
Jean-Pierre Brion
Keyword(s):  
Neurofibrillary Tangles ◽  
Tau Protein

scholarly journals A Protein Kinase, PKN, Accumulates in Alzheimer Neurofibrillary Tangles and Associated Endoplasmic Reticulum-Derived Vesicles and Phosphorylates Tau Protein

1998 ◽  
Vol 18 (18) ◽  
pp. 7402-7410 ◽  
Author(s):  
Toshio Kawamata ◽  
Taizo Taniguchi ◽  
Hideyuki Mukai ◽  
Michinori Kitagawa ◽  
Takeshi Hashimoto ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Neurofibrillary Tangles ◽  
Tau Protein ◽  
Alzheimer Neurofibrillary Tangles

Intracellular Responses of Glial Cells To Monomeric Tau Protein Are Closely Mediated By Heparan Sulfate Proteoglycans (HSPGs)

2021 ◽  
Author(s):  
Liqing Song ◽  
Daniel E. Oseid ◽  
Evan A. Wells ◽  
Troy Coaston ◽  
Anne S Robinson
Keyword(s):  
Gene Expression ◽  
Heparan Sulfate ◽  
Glial Cells ◽  
Neurofibrillary Tangles ◽  
Tau Protein ◽  
Intracellular Signaling ◽  
Heparan Sulfate Proteoglycans ◽  
C6 Glioma Cells ◽  
Dependent Manner

Abstract The conversion of soluble tau protein to insoluble, hyperphosphorylated neurofibrillary tangles is a major hallmark leading to neuronal death observed in neurodegenerative tauopathies. Recent work suggests that extracellular, soluble tau binds to negatively charged heparan sulfate proteoglycans (HSPGs) available on the cell surface. In addition, LRP1 has recently been recognized as a major tau receptor, mediating tau uptake and spread. We hypothesized based on this data that monomeric tau would be endocytosed in both an HSPG- and LRP-dependent manner, activating intracellular signaling pathways that would regulate cellular phenotypes. Using live-cell confocal microscopy and flow cytometry, we show that soluble 0N4R monomers were rapidly endocytosed by SH-SY5Y and C6 glioma cells, via actin-dependent macropinocytosis. We also demonstrated the crucial role of HSPGs and LRP1 in cellular endocytosis of monomeric tau by observing reduced tau uptake in C6 glial cells with genetic knockouts of xylosyltransferase-1 – a key enzyme in HSPG synthesis – and LRP1. An ERK1/2 inhibition experiment showed that inhibiting the MEK-ERK1/2 signaling pathway attenuated IL-6 and IL-1β gene expression but not TNF-α . An LRP1 knockdown experiment led to an attenuated propensity for tau uptake and further elevated IL-6 gene expression. Collectively, our data suggest that tau has multiple extracellular binding partners that mediate its internalization through distinct mechanisms. Additionally, this study demonstrates the important role of both HSPG and LRP1 in regulating cellular immune responses to tau protein monomer, which provides a novel target for alleviating the neuroinflammatory environment before the formation of neurofibrillary tangles.

Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein

10.1038/78078 ◽  
2000 ◽  
Vol 25 (4) ◽  
pp. 402-405 ◽  
Author(s):  
Jada Lewis ◽  
Eileen McGowan ◽  
Julia Rockwood ◽  
Heather Melrose ◽  
Parimala Nacharaju ◽  
...  
Keyword(s):  
Neurofibrillary Tangles ◽  
Tau Protein ◽  
Motor Disturbance

scholarly journals Tau aggregates possibly compromise neuronal health in the C. elegans model of Alzheimer’s disease

2020 ◽  
Vol 1 (6) ◽  
pp. 46-48
Author(s):  
Sanjib Guha ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Tau Protein ◽  
Intercellular Space ◽  
Senile Plaques ◽  
Aβ Peptide ◽  
Progressive Decline ◽  
C Elegans ◽  
Model Of Alzheimer’S Disease

Alzheimer’s disease (AD) is the most common degenerative brain disease in the aged population [1]. By 2050, AD prevalence is expected to increase from 4.7 million (based on 2010 census) to 13.8 million people [2]. It is characterized by the progressive decline of cognition and memory, as well as changes in behavior and personality [1]. Pathological hallmarks of AD include mainly formation of senile plaques consisting of amyloid-beta (Aβ) peptide in the intercellular space and neurofibrillary tangles (NFTs) in the cell bodies, which are primarily composed of abnormally modified tau protein [3].

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