Osthole decreases tau protein phosphorylation via PI3K/AKT/GSK-3β signaling pathway in Alzheimer's disease

Life Sciences ◽  
2019 ◽  
Vol 217 ◽  
pp. 16-24 ◽  
Author(s):  
Yingjia Yao ◽  
Yameng Wang ◽  
Liang Kong ◽  
Yuqing Chen ◽  
Jingxian Yang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Phosphorylation ◽  
Signaling Pathway ◽  
Tau Protein ◽  
Gsk 3Β

scholarly journals A current view on Tau protein phosphorylation in Alzheimer's disease

2021 ◽  
Vol 69 ◽  
pp. 131-138
Author(s):  
Susanne Wegmann ◽  
Jacek Biernat ◽  
Eckhard Mandelkow
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Phosphorylation ◽  
Tau Protein ◽  
Current View ◽  
A Current

scholarly journals Schisantherin A Improves the Learning and Memory by Reducing the Phosphorylation of Tau Protein of the Hippocampus in AD Mice

2020 ◽  
Vol 15 (3) ◽  
pp. 1934578X1990068
Author(s):  
Shu Jing ◽  
Cong Liu ◽  
Huijiao Lin ◽  
Xinyun Zhang ◽  
Fei Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Tau Protein ◽  
Glycogen Synthase ◽  
Learning Ability ◽  
Morris Water Maze Test ◽  
Amyloid Β Protein ◽  
Gsk 3Β ◽  
Schisantherin A

Memory disorders are the main symptoms of aging and Alzheimer’s disease and seriously affect the quality of life. Schisandra, as a famous traditional Chinese medicine, has been used for modulating “the internal organs” for a thousand years. The total lignans from Schisandra have been scientifically proved to improve learning and memory ability. Since it is unclear which monomer in Schisandra total lignans exerts such a function, we evaluated the potential effects of Schisantherin A (SCA), the main monomer from Schisandra, on improving learning ability and memory in amyloid β-protein (Aβ1-42)-induced Alzheimer’s disease (AD) model mice. We found that SCA (5 mg/kg) significantly prolonged the latency and reduced the number of errors in a step-through test. SCA significantly shortened the time of finding the platform and increased the number of crossing the platform and the residence time in a Morris water maze test. SCA increased superoxide dismutase activities and reduced the Malondialdehyde level of the hippocampal tissue, suggesting its role in reducing oxidative stress in the AD mice. Furthermore, we found that SCA significantly decreased the hyperphosphorylation of Tau by altering glycogen synthase kinase-3β (GSK-3β) phosphorylation on Tyr216 and Ser9. Our results revealed the mechanism underlying SCA-mediated learning and memory improvement by regulating GSK-3β activity and lowering the hyperphosphorylation of Tau protein in the hippocampus of AD mice.

scholarly journals Lithium inhibits Alzheimer's disease-like tau protein phosphorylation in neurons

FEBS Letters ◽  
1997 ◽  
Vol 411 (2-3) ◽  
pp. 183-188 ◽  
Author(s):  
Juan Ramón Muñoz-Montaño ◽  
Francisco J. Moreno ◽  
Jesús Avila ◽  
Javier Dı́az-Nido
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Phosphorylation ◽  
Tau Protein

Inhibiting α1-adrenergic Receptor Signaling Pathway Ameliorates Alzheimer’s Disease Type Pathologies and Behavioral Deficits in an AD Mouse Model

2021 ◽  
Author(s):  
Zhong-Yuan Yu ◽  
Xu Yi ◽  
Ye-Ran Wang ◽  
Gui-Hua Zeng ◽  
Cheng-Rong Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Neuronal Loss ◽  
Behavioral Deficits ◽  
Bace1 Expression ◽  
Receptor Signaling Pathway ◽  
Gsk 3Β

Abstract Background The role of α1 adrenergic receptors (α1-ARs) signaling pathway in the pathogenesis of Alzheimer’s disease (AD) has rarely been investigated. Clarifying pathophysiological functions of α1-ARs in the AD brain is helpful for better understanding the pathogenesis and screening novel therapeutic target of AD. Methods This study included 2 arms of in vivo investigations: 1) 6-month-old female APPswe/PS1 mice were intravenously treated with AAV-PHP.eB-shRNA (ARs)-GFP or AAV-PHP.eB-GFP for 3 months. 2) 3-month-old female APPswe/PS1 mice were daily treated with 0.5 mg/kg terazosin or equal saline for 6 months. SH-SY5Y cell lines bearing human Amyloid precurssor protein were treated with terazosin or saline for investigating possible mechanisms. Results α1-ARs knockdown mice exhibited improved behavioral performances than control mice. α1-ARs knockdown mice had significantly lower brain amyloid burden, as reflected by soluble Aβ species, compact and total plaques, than control mice. The α1-ARs inhibitor terazosin substantially reduced Aβ deposition, attenuated downstream pathologies including Tau hyperphosphorylation, glial activation, neuronal loss, synaptic dysfunction, and rescued behavioral deficits of APPswe/PS1 mice. In vitro investigation demonstrated that α1-ARs inhibition down-regulated BACE1 expression, and promoted ser9 phosphorylation of GSK-3β, thus reduced Aβ production. Conclusions This study indicates that inhibition of α1-ARs signaling pathway might represent a promising therapeutic strategy for AD.

Quantitative analysis of tau protein in paired helical filament preparations: Implications for the role of tau protein phosphorylation in PHF assembly in Alzheimer's disease

1995 ◽  
Vol 16 (3) ◽  
pp. 409-417 ◽  
Author(s):  
Claude M. Wischik ◽  
Patricia C. Edwards ◽  
Robert Y.K. Lai ◽  
Herman N.-J. Gertz ◽  
John H. Xuereb ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Quantitative Analysis ◽  
Protein Phosphorylation ◽  
Tau Protein ◽  
Paired Helical Filament

scholarly journals Antioxidant, Anti-inflammatory and Neuroprotective Profiles of Novel 1,4-Dihydropyridine Derivatives for the Treatment of Alzheimer’s Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 650
Author(s):  
Patrycja Michalska ◽  
Paloma Mayo ◽  
Cristina Fernández-Mendívil ◽  
Giammarco Tenti ◽  
Pablo Duarte ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Hippocampal Slices ◽  
Antioxidant Properties ◽  
Neuronal Loss ◽  
Pathological Process ◽  
Anti Inflammatory ◽  
Gsk 3Β

Alzheimer’s disease is a chronic and irreversible pathological process that has become the most prevalent neurodegenerative disease. Currently, it is considered a multifactorial disease where oxidative stress and chronic neuroinflammation play a crucial role in its onset and development. Its characteristic neuronal loss has been related to the formation of neurofibrillary tangles mainly composed by hyperphosphorylated tau protein. Hyperphosphorylation of tau protein is related to the over-activity of GSK-3β, a kinase that participates in several pathological mechanisms including neuroinflammation. Neuronal loss is also related to cytosolic Ca2+ homeostasis dysregulation that triggers apoptosis and free radicals production, contributing to oxidative damage and, finally, neuronal death. Under these premises, we have obtained a new family of 4,7-dihydro-2H-pyrazolo[3–b]pyridines as multitarget directed ligands showing potent antioxidant properties and able to scavenge both oxygen and nitrogen radical species, and also, with anti-inflammatory properties. Further characterization has demonstrated their capacity to inhibit GSK-3β and to block L-type voltage dependent calcium channels. Novel derivatives have also demonstrated an interesting neuroprotective profile on in vitro models of neurodegeneration. Finally, compound 4g revokes cellular death induced by tau hyperphosphorylation in hippocampal slices by blocking reactive oxygen species (ROS) production. In conclusion, the multitarget profile exhibited by these compounds is a novel therapeutic strategy of potential interest in the search of novel treatments for Alzheimer’s disease.

Alzheimer's disease skin fibroblasts selectively express a bradykinin signaling pathway mediating tau protein Ser phosphorylation

2003 ◽  
Vol 17 (15) ◽  
pp. 2319-2321 ◽  
Author(s):  
Yuh-Jiin I. Jong ◽  
Stephanie R. Ford ◽  
Kuljeet Seehra ◽  
Victor Brian Malave ◽  
Nancy Lewis Baenziger
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Tau Protein ◽  
Skin Fibroblasts

Interleukin-1 promotion of MAPK-p38 overexpression in experimental animals and in Alzheimer's disease: potential significance for tau protein phosphorylation

2001 ◽  
Vol 39 (5-6) ◽  
pp. 341-348 ◽  
Author(s):  
Jin G. Sheng ◽  
Richard A. Jones ◽  
Xue Q. Zhou ◽  
John M. McGinness ◽  
Linda J. Van Eldik ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Phosphorylation ◽  
Tau Protein ◽  
Interleukin 1 ◽  
Potential Significance ◽  
Experimental Animals
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