scholarly journals Methylene Blue Blocks and Reverses the Inhibitory Effect of Tau on PMCA Function

2019 ◽  
Vol 20 (14) ◽  
pp. 3521 ◽  
Author(s):  
Maria Berrocal ◽  
Montaña Caballero-Bermejo ◽  
Carlos Gutierrez-Merino ◽  
Ana M. Mata
Keyword(s):  
Methylene Blue ◽  
Plasma Membrane ◽  
Molecular Marker ◽  
Cell Cultures ◽  
Calcium Homeostasis ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Therapeutic Drug ◽  
Amyloid Β Peptide ◽  
Molecular Mechanism Of Action

Methylene blue (MB) is a synthetic phenothiazine dye that, in the last years, has generated much debate about whether it could be a useful therapeutic drug for tau-related pathologies, such as Alzheimer’s disease (AD). However, the molecular mechanism of action is far from clear. Recently we reported that MB activates the plasma membrane Ca2+-ATPase (PMCA) in membranes from human and pig tissues and from cells cultures, and that it could protect against inactivation of PMCA by amyloid β-peptide (Aβ). The purpose of the present study is to further examine whether the MB could also modulate the inhibitory effect of tau, another key molecular marker of AD, on PMCA activity. By using kinetic assays in membranes from several tissues and cell cultures, we found that this phenothiazine was able to block and even to completely reverse the inhibitory effect of tau on PMCA. The results of this work point out that MB could mediate the toxic effect of tau related to the deregulation of calcium homeostasis by blocking the impairment of PMCA activity by tau. We then could conclude that MB could interfere with the toxic effects of tau by restoring the function of PMCA pump as a fine tuner of calcium homeostasis.

Impairment of the activity of the plasma membrane Ca2+-ATPase in Alzheimer's disease

2011 ◽  
Vol 39 (3) ◽  
pp. 819-822 ◽  
Author(s):  
Ana M. Mata ◽  
María Berrocal ◽  
M. Rosario Sepúlveda
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Amyloid Β Peptide ◽  
Aβ Amyloid

AD (Alzheimer's disease) is an age-associated neurodegenerative disorder where the accumulation of neurotoxic Aβ (amyloid β-peptide) in senile plaques is a typical feature. Recent studies point out a relationship between Aβ neurotoxicity and Ca2+ dyshomoeostasis, but the molecular mechanisms involved are still under discussion. The PMCAs (plasma membrane Ca2+-ATPases) are a multi-isoform family of proteins highly expressed in brain that is implicated in the maintenance of low intraneural Ca2+ concentration. Therefore the malfunction of this pump may also be responsible for Ca2+ homoeostasis failure in AD. We have found that the Ca2+-dependence of PMCA activity is affected in human brains diagnosed with AD, being related to the enrichment of Aβ. The peptide produces an inhibitory effect on the activity of PMCA which is isoform-specific, with the greatest inhibition of PMCA4. Besides, cholesterol blocked the inhibitory effect of Aβ, which is consistent with the lack of any Aβ effect on PMCA4 found in cholesterol-enriched lipid rafts isolated from pig brain. These observations suggest that PMCAs are a functional component of the machinery that leads to Ca2+ dysregulation in AD and propose cholesterol enrichment in rafts as a protector of the Aβ-mediated inhibition on PMCA.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

Synaptic Silencing and Plasma Membrane Dyshomeostasis Induced by Amyloid-β Peptide are Prevented by Aristotelia chilensis Enriched Extract

2012 ◽  
Vol 31 (4) ◽  
pp. 879-889 ◽  
Author(s):  
Jorge Fuentealba ◽  
Andrea Dibarrart ◽  
Francisco Saez-Orellana ◽  
María Cecilia Fuentes-Fuentes ◽  
Carlos N. Oyanedel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Aristotelia Chilensis

Val8-GLP-1 remodels synaptic activity and intracellular calcium homeostasis impaired by amyloid β peptide in rats

2013 ◽  
Vol 91 (4) ◽  
pp. 568-577 ◽  
Author(s):  
Xiao-Hui Wang ◽  
Wei Yang ◽  
Christian Hölscher ◽  
Zhao-Jun Wang ◽  
Hong-Yan Cai ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Homeostasis ◽  
Amyloid Β ◽  
Synaptic Activity ◽  
Amyloid Β Peptide ◽  
Intracellular Calcium Homeostasis

scholarly journals Amyloid Beta Peptide (Aβ1-42) Reverses the Cholinergic Control of Monocytic IL-1β Release

2020 ◽  
Vol 9 (9) ◽  
pp. 2887
Author(s):  
Katrin Richter ◽  
Raymond Ogiemwonyi-Schaefer ◽  
Sigrid Wilker ◽  
Anna I. Chaveiro ◽  
Alisa Agné ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Mononuclear Leukocytes ◽  
Amyloid Β Peptide ◽  
Monocytic Cells ◽  
Cholinergic Mechanism ◽  
Beta Peptide ◽  
Α7 Nicotinic Acetylcholine Receptors

Amyloid-β peptide (Aβ1-42), the cleavage product of the evolutionary highly conserved amyloid precursor protein, presumably plays a pathogenic role in Alzheimer’s disease. Aβ1-42 can induce the secretion of the pro-inflammatory cytokine intereukin-1β (IL-1β) in immune cells within and out of the nervous system. Known interaction partners of Aβ1-42 are α7 nicotinic acetylcholine receptors (nAChRs). The physiological functions of Aβ1-42 are, however, not fully understood. Recently, we identified a cholinergic mechanism that controls monocytic release of IL-1β by canonical and non-canonical agonists of nAChRs containing subunits α7, α9, and/or α10. Here, we tested the hypothesis that Aβ1-42 modulates this inhibitory cholinergic mechanism. Lipopolysaccharide-primed monocytic U937 cells and human mononuclear leukocytes were stimulated with the P2X7 receptor agonist 2′(3′)-O-(4-benzoylbenzoyl)adenosine-5′-triphosphate triethylammonium salt (BzATP) in the presence or absence of nAChR agonists and Aβ1-42. IL-1β concentrations were measured in the supernatant. Aβ1-42 dose-dependently (IC50 = 2.54 µM) reversed the inhibitory effect of canonical and non-canonical nicotinic agonists on BzATP-mediated IL-1β-release by monocytic cells, whereas reverse Aβ42-1 was ineffective. In conclusion, we discovered a novel pro-inflammatory Aβ1-42 function that enables monocytic IL-1β release in the presence of nAChR agonists. These findings provide evidence for a novel physiological function of Aβ1-42 in the context of sterile systemic inflammation.

Methylene blue activates the PMCA activity and cross-interacts with amyloid β-peptide, blocking Aβ-mediated PMCA inhibition

2018 ◽  
Vol 139 ◽  
pp. 163-172 ◽  
Author(s):  
Maria Berrocal ◽  
Isaac Corbacho ◽  
Carlos Gutierrez-Merino ◽  
Ana M. Mata
Keyword(s):  
Methylene Blue ◽  
Amyloid Β ◽  
Amyloid Β Peptide

scholarly journals Inhibition of DNA synthesis in SV3T3 cultures by isolated 3T3 plasma membranes.

1983 ◽  
Vol 97 (1) ◽  
pp. 276-279 ◽  
Author(s):  
S W Peterson ◽  
V Lerch
Keyword(s):  
Plasma Membrane ◽  
Dna Synthesis ◽  
Cell Cultures ◽  
Plasma Membranes ◽  
Inhibitory Effect ◽  
Density Dependent ◽  
Inhibition Of Growth ◽  
Dependent Inhibition ◽  
Membrane Components ◽  
Inhibition Of Dna Synthesis

3T3 plasma membranes were added to subconfluent cultures of SV3T3 cells in the presence of fusogens. If this protocol results in the introduction into the SV3T3 cell membrane of 3T3 plasma membrane components responsible for density-dependent inhibition of growth, then the SV3T3 cell cultures would be expected to show decreased rates of DNA synthesis as they approach confluence. Results of these experiments indicate that rates of DNA synthesis in SV3T3 cultures so treated were as much as 63% less than in untreated controls. This effect could not be attributed to the fusogens or to the 3T3 plasma membranes alone. This growth-inhibitory effect is specific for 3T3 membranes and is not observed when SV3T3 plasma membranes are fused with SV3T3 cell cultures. These data support the hypothesis that one aspect of the loss of density-dependent inhibition of growth in SV3T3 cells is a deletion or alteration in plasma membrane components and, further, that density-dependent inhibition of growth can be in part restored to SV3T3 cell cultures by fusing the cells with 3T3 plasma membranes.

scholarly journals Dieckol Ameliorates Aβ Production via PI3K/Akt/GSK-3β Regulated APP Processing in SweAPP N2a Cell

Marine Drugs ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 152
Author(s):  
Jeong-Hyun Yoon ◽  
Nayoung Lee ◽  
Kumju Youn ◽  
Mi Ra Jo ◽  
Hyeung-Rak Kim ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Inhibitory Effect ◽  
Proteolytic Processing ◽  
Amyloid Β Peptide ◽  
Phosphatidylinositol 3 Kinase ◽  
App Processing ◽  
Pi3k Inhibitor Ly294002 ◽  
Processing Enzymes ◽  
Gsk 3Β ◽  
Aβ Production

The proteolytic processing of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase releases amyloid-β peptide (Aβ), which deposits in amyloid plaques and contributes to the initial causative events of Alzheimer’s disease (AD). In the present study, the regulatory mechanism of APP processing of three phlorotannins was elucidated in Swedish mutant APP overexpressed N2a (SweAPP N2a) cells. Among the tested compounds, dieckol exhibited the highest inhibitory effect on both intra- and extracellular Aβ accumulation. In addition, dieckol regulated the APP processing enzymes, such as α-secretase (ADAM10), β-secretase, and γ-secretase, presenilin-1 (PS1), and their proteolytic products, sAPPα and sAPPβ, implying that the compound acts on both the amyloidogenic and non-amyloidogenic pathways. In addition, dieckol increased the phosphorylation of protein kinase B (Akt) at Ser473 and GSK-3β at Ser9, suggesting dieckol induced the activation of Akt, which phosphorylated GSK-3β. The specific phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 triggered GSK-3β activation and Aβ expression. In addition, co-treatment with LY294002 noticeably blocked the effect of dieckol on Aβ production, demonstrating that dieckol promoted the PI3K/Akt signaling pathway, which in turn inactivated GSK-3β, resulting in the reduction in Aβ levels.

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