3×Tg-AD Mice Overexpressing Phospholipid Transfer Protein Improves Cognition Through Decreasing Amyloid-β Production and Tau Hyperphosphorylation

2021 ◽  
pp. 1-15
Author(s):  
Wen-Zhi Wang ◽  
Ming-Wei Li ◽  
Ying Chen ◽  
Li-Yuan Liu ◽  
Yong Xu ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Tau Phosphorylation ◽  
Phospholipid Transfer Protein ◽  
Lipid Transfer ◽  
Neuroprotective Effects ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Exact Effect

Background: Phospholipid transfer protein (PLTP) belongs to the lipid transfer glycoprotein family. Studies have shown that it is closely related to Alzheimer’s disease (AD); however, the exact effect and mechanism remain unknown. Objective: To observe the effect of PLTP overexpression on behavioral dysfunction and the related mechanisms in APP/PS1/Tau triple transgenic (3×Tg-AD) mice. Methods: AAV-PLTP-EGFP was injected into the lateral ventricle to induce PLTP overexpression. The memory of 3×Tg-AD mice and wild type (WT) mice aged 10 months were assessed using Morris water maze (MWM) and shuttle-box passive avoidance test (PAT). Western blotting and ELISA assays were used to quantify the protein contents. Hematoxylin and eosin, Nissl, and immunochemistry staining were utilized in observing the pathological changes in the brain. Results: 3×Tg-AD mice displayed cognitive impairment in WMW and PAT, which was ameliorated by PLTP overexpression. The histopathological hallmarks of AD, senile plaques and neurofibrillary tangles, were observed in 3×Tg-AD mice and were improved by PLTP overexpression. Besides, the increase of amyloid-β42 (Aβ 42) and Aβ 40 were found in the cerebral cortex and hippocampus of 3×Tg-AD mice and reversed by PLTP overexpression through inhibiting APP and PS1. PLTP overexpression also reversed tau phosphorylation at the Ser404, Thr231 and Ser199 of the hippocampus in 3×Tg-AD mice. Furthermore, PLTP overexpression induced the glycogen synthase kinase 3β (GSK3β) inactivation via upregulating GSK3β (pSer9). Conclusion: These results suggest that PLTP overexpression has neuroprotective effects. These effects are possibly achieved through the inhibition of the Aβ production and tau phosphorylation, which is related to GSK3β inactivation.

scholarly journals Regulation and Essentiality of the StAR-related Lipid Transfer (START) Domain-containing Phospholipid Transfer Protein PFA0210c in Malaria Parasites

2016 ◽  
Vol 291 (46) ◽  
pp. 24280-24292 ◽  
Author(s):  
Ross J. Hill ◽  
Alessa Ringel ◽  
Ellen Knuepfer ◽  
Robert W. Moon ◽  
Michael J. Blackman ◽  
...  
Keyword(s):  
Phospholipid Transfer Protein ◽  
Lipid Transfer ◽  
Malaria Parasites ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Start Domain

Interfacial and lipid transfer properties of human phospholipid transfer protein

2007 ◽  
Vol 149 ◽  
pp. S88-S89
Author(s):  
Niko Setälä ◽  
Jari Metso ◽  
Susanne Wiedmer ◽  
Gebrenegus Yohannes ◽  
Paavo Kinnunen ◽  
...  
Keyword(s):  
Phospholipid Transfer Protein ◽  
Lipid Transfer ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Transfer Properties

Interfacial and Lipid Transfer Properties of Human Phospholipid Transfer Protein:  Implications for the Transfer Mechanism of Phospholipids†

Biochemistry ◽  
2007 ◽  
Vol 46 (5) ◽  
pp. 1312-1319 ◽  
Author(s):  
Niko L. Setälä ◽  
Juha M. Holopainen ◽  
Jari Metso ◽  
Susanne K. Wiedmer ◽  
Gebrenegus Yohannes ◽  
...  
Keyword(s):  
Transfer Mechanism ◽  
Phospholipid Transfer Protein ◽  
Lipid Transfer ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Transfer Properties

Abstract 127: Structure and Function Relationship of Phospholipid Transfer Protein in Lipid Transfer Activity Revealed by Electron Microscopy

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Meng Zhang
Keyword(s):  
Electron Microscopy ◽  
High Density Lipoproteins ◽  
Phospholipid Transfer Protein ◽  
Lipid Transfer ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function ◽  
Relationship Of

Human phospholipid transfer protein (PLTP) mediates the transfer of lipids among atheroprotective high-density lipoproteins (HDL) and atherogenic low-density lipoproteins (LDL) by an unknown mechanism. Delineating this mechanism would be an important step toward the understanding and regulation of PLTP for treating cardiovascular diseases, hypoalphalipoproteinemia and hyperalphalipoproteinemia. Using electron microscopy, negative-staining, and single-particle image processing, we discovered that PLTP penetrates each class of HDL, LDL and liposome independently, and also bridges a ternary complex with one of its distal end-domains penetrating into HDL and another distal domain interacting with LDL. These new insights into PLTP interaction with lipoproteins and liposomes provide a molecular basis for analyzing PLTP-dependent lipid transfer between lipoprotein particles.

scholarly journals Increased Amyloid-β Peptide-Induced Memory Deficits in Phospholipid Transfer Protein (PLTP) Gene Knockout Mice

2012 ◽  
Vol 38 (5) ◽  
pp. 817-825 ◽  
Author(s):  
Catherine Desrumaux ◽  
Amandine Pisoni ◽  
Johann Meunier ◽  
Valérie Deckert ◽  
Anne Athias ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Gene Knockout ◽  
Amyloid Β ◽  
Memory Deficits ◽  
Amyloid Β Peptide ◽  
Phospholipid Transfer Protein ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Gene Knockout Mice

Evaluation of phospholipid transfer protein and cholesteryl ester transfer protein as contributors to the generation of preβ-high-density lipoproteins

2001 ◽  
Vol 360 (2) ◽  
pp. 379-385 ◽  
Author(s):  
Jessica LIE ◽  
Rini de CROM ◽  
Matti JAUHIAINEN ◽  
Teus van GENT ◽  
Rien van HAPEREN ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Reverse Cholesterol Transport ◽  
High Density Lipoproteins ◽  
Cholesterol Transport ◽  
Phospholipid Transfer Protein ◽  
Lipid Transfer ◽  
Wild Type ◽  
Lipid Transfer Proteins ◽  
Transfer Protein ◽  
Phospholipid Transfer

High-density lipoproteins (HDLs) are considered anti-atherogenic because they mediate peripheral cell cholesterol transport to the liver for excretion and degradation. An important step in this reverse cholesterol-transport pathway is the uptake of cellular cholesterol by a specific subclass of small, lipid-poor apolipoprotein A-I particles designated preβ-HDL. The two lipid-transfer proteins present in human plasma, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), have both been implicated in the formation of preβ-HDL. In order to investigate the relative contribution of each of these proteins, we used transgenic mouse models. Comparisons were made between human CETP transgenic mice (huCETPtg), human PLTP transgenic mice (huPLTPtg) and mice transgenic for both lipid-transfer proteins (huCETPtg/huPLTPtg). These animals showed elevated plasma levels of CETP activity, PLTP activity or both activities, respectively. We evaluated the generation of preβ-HDL in mouse plasma by immunoblotting and crossed immuno-electrophoresis. Generation of preβ-HDL was equal in huCETPtg and wild-type mice. In contrast, in huPLTPtg and huCETPtg/huPLTPtg mice, preβ-HDL generation was 3-fold higher than in plasma from either wild-type or huCETPtg mice. Our findings demonstrate that, of the two plasma lipid-transfer proteins, PLTP rather than CETP is responsible for the generation of preβ-HDL. These data support the hypothesis of a role for PLTP in the initial stage of reverse cholesterol transport.

Sign in / Sign up

Export Citation Format

Share Document