scholarly journals Cornel Iridoid Glycoside Attenuates Tau Hyperphosphorylation by Inhibition of PP2A Demethylation

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Cui-cui Yang ◽  
Xue-xian Kuai ◽  
Ya-li Li ◽  
Li Zhang ◽  
Jian-chun Yu ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Glycogen Synthase ◽  
Iridoid Glycoside ◽  
Tau Hyperphosphorylation ◽  
Human Neuroblastoma ◽  
Microtubular Cytoskeleton ◽  
Gf 109203X ◽  
Phosphatase 2A ◽  
Cornel Iridoid Glycoside ◽  
Underlying Mechanisms

Aim. The aim of the present study was to investigate the effect of cornel iridoid glycoside (CIG) on tau hyperphosphorylation induced by wortmannin (WT) and GF-109203X (GFX) and the underlying mechanisms.Methods. Human neuroblastoma SK-N-SH cells were preincubated with CIG (50, 100, and 200 µg/ml, resp.) for 24 h and then exposed to 10 µM WT and 10 µM GFX for 3 h after washing out CIG. Immunohistochemistry was used to observe the microtubular cytoskeleton of the cultured cells. Western blotting was used to measure the phosphorylation level of tau protein, glycogen synthase kinase 3β(GSK-3β), and protein phosphatase 2A (PP2A). The activity of PP2A was detected by a biochemical assay.Results. Preincubation of CIG significantly attenuated the WT/GFX-induced tau hyperphosphorylation at the sites of Thr205, Thr212, Ser214, Thr217, Ser396, and PHF-1 and improved the damage of morphology and microtubular cytoskeleton of the cells. CIG did not prevent the decrease in p-AKT-ser473 and p-GSK-3β-ser9 induced by WT/GFX. However, CIG significantly elevated the activity of PP2A by reducing the demethylation of PP2A catalytic subunit (PP2Ac) at Leu309 and the ratio of PME-1/LCMT in the WT/GFX-treated cells. The results suggest that CIG may be beneficial to the treatment of AD.

Cornel Iridoid Glycoside Suppresses Tau Hyperphosphorylation and Aggregation in a Mouse Model of Tauopathy through Increasing Activity of PP2A

2020 ◽  
Vol 16 (14) ◽  
pp. 1316-1331 ◽  
Author(s):  
Denglei Ma ◽  
Yi Luo ◽  
Rui Huang ◽  
Zirun Zhao ◽  
Qi Wang ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Chinese Herb ◽  
Iridoid Glycoside ◽  
Synaptic Proteins ◽  
Intragastric Administration ◽  
Tau Hyperphosphorylation ◽  
Phosphatase 2A ◽  
Cornel Iridoid Glycoside ◽  
The Brain

Background: rTg4510 mice are transgenic mice expressing P301L mutant tau and have been developed as an animal model of tauopathy including Alzheimer’s Disease (AD). Cornel Iridoid Glycoside (CIG) is an active ingredient extracted from Cornus officinalis, a traditional Chinese herb. The purpose of the present study was to investigate the effects of CIG on tau pathology and underlying mechanisms using rTg4510 mice. Methods: The cognitive functions were detected by Morris water maze and objective recognition tests. Western blotting and immunofluorescence were conducted to measure the levels of phosphorylated tau and related proteins. Serine/threonine phosphatase assay was applied to detect the activity of protein phosphatase 2A (PP2A). Results: Intragastric administration of CIG for 3 months improved learning and memory abilities, prevented neuronal and synapse loss, halted brain atrophy, elevated levels of synaptic proteins, protected cytoskeleton, reduced tau hyperphosphorylation and aggregation in the brain of rTg4510 mice. In the mechanism studies, CIG increased the activity of PP2A, elevated the methylation of PP2A catalytic C (PP2Ac) at leucine 309, decreased the phosphorylation of PP2Ac at tyrosine 307, and increased protein expression of leucine carboxyl methyltransferase 1 (LCMT-1), protein tyrosine phosphatase 1B (PTP1B), and protein phosphatase 2A phosphatase activator (PTPA) in the brain of rTg4510 mice. Conclusion: CIG might have the potential to treat tauopathy such as AD via activating PP2A.

Targeting Tau Hyperphosphorylation via Kinase Inhibition: Strategy to Address Alzheimer's Disease

2020 ◽  
Vol 20 (12) ◽  
pp. 1059-1073 ◽  
Author(s):  
Ahmad Abu Turab Naqvi ◽  
Gulam Mustafa Hasan ◽  
Md. Imtaiyaz Hassan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Glycogen Synthase ◽  
Paired Helical Filaments ◽  
Tau Hyperphosphorylation ◽  
Microtubule Stabilization ◽  
Extracellular Signal

Microtubule-associated protein tau is involved in the tubulin binding leading to microtubule stabilization in neuronal cells which is essential for stabilization of neuron cytoskeleton. The regulation of tau activity is accommodated by several kinases which phosphorylate tau protein on specific sites. In pathological conditions, abnormal activity of tau kinases such as glycogen synthase kinase-3 β (GSK3β), cyclin-dependent kinase 5 (CDK5), c-Jun N-terminal kinases (JNKs), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and microtubule affinity regulating kinase (MARK) lead to tau hyperphosphorylation. Hyperphosphorylation of tau protein leads to aggregation of tau into paired helical filaments like structures which are major constituents of neurofibrillary tangles, a hallmark of Alzheimer’s disease. In this review, we discuss various tau protein kinases and their association with tau hyperphosphorylation. We also discuss various strategies and the advancements made in the area of Alzheimer's disease drug development by designing effective and specific inhibitors for such kinases using traditional in vitro/in vivo methods and state of the art in silico techniques.

Restricted growth of attenuated poliovirus strains in cultured cells of a human neuroblastoma.

1989 ◽  
Vol 63 (9) ◽  
pp. 4034-4038 ◽  
Author(s):  
V I Agol ◽  
S G Drozdov ◽  
T A Ivannikova ◽  
M S Kolesnikova ◽  
M B Korolev ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Human Neuroblastoma
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