Apolipoprotein E Mimetic Peptides: Cholesterol-Dependent and Cholesterol-Independent Properties

2015 ◽  
pp. 135-156 ◽  
Author(s):  
David W. Garber ◽  
Dennis Goldberg ◽  
G. M. Anantharamaiah
Keyword(s):  
Apolipoprotein E ◽  
Mimetic Peptides

scholarly journals Two apolipoprotein E mimetic peptides with similar cholesterol reducing properties exhibit differential atheroprotective effects in LDL-R null mice

2013 ◽  
Vol 227 (1) ◽  
pp. 58-64 ◽  
Author(s):  
Shaila P. Handattu ◽  
Gaurav Nayyar ◽  
David W. Garber ◽  
Mayakonda N. Palgunachari ◽  
Candyce E. Monroe ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Mimetic Peptides ◽  
Reducing Properties

Protective effect of apolipoprotein E-mimetic peptides on N-methyl-d-aspartate excitotoxicity in primary rat neuronal–glial cell cultures

Neuroscience ◽  
2003 ◽  
Vol 116 (2) ◽  
pp. 437-445 ◽  
Author(s):  
M Aono ◽  
E.R Bennett ◽  
K.S Kim ◽  
J.R Lynch ◽  
J Myers ◽  
...  
Keyword(s):  
Protective Effect ◽  
Apolipoprotein E ◽  
Glial Cell ◽  
Cell Cultures ◽  
Mimetic Peptides ◽  
Glial Cell Cultures

The future of apolipoprotein E mimetic peptides in the prevention of cardiovascular disease

2019 ◽  
Vol 30 (4) ◽  
pp. 326-341 ◽  
Author(s):  
Eftaxia-Konstantina Valanti ◽  
Angeliki Chroni ◽  
Despina Sanoudou
Keyword(s):  
Cardiovascular Disease ◽  
Apolipoprotein E ◽  
Mimetic Peptides ◽  
The Future ◽  
Prevention Of Cardiovascular Disease

scholarly journals HDL mimetic peptides affect apolipoprotein E metabolism: equal supplement or functional enhancer?

2018 ◽  
Vol 147 (5) ◽  
pp. 580-583 ◽  
Author(s):  
Wenzhang Wang ◽  
Xiongwei Zhu
Keyword(s):  
Apolipoprotein E ◽  
Mimetic Peptides

Two Apolipoprotein E Mimetic Peptides, ApoE(130−149) and ApoE(141−155)2, Bind to LRP1†

Biochemistry ◽  
2004 ◽  
Vol 43 (23) ◽  
pp. 7328-7335 ◽  
Author(s):  
Johnny E. Croy ◽  
Theodore Brandon ◽  
Elizabeth A. Komives
Keyword(s):  
Apolipoprotein E ◽  
Mimetic Peptides

Apolipoprotein E-Mimetic Therapeutic Peptides Mediate CLL Cell Cytotoxicity

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 359-359
Author(s):  
Dale J. Christensen ◽  
Karen M. Bond ◽  
Alicia D. Volkheimer ◽  
Jessica Oddo ◽  
Youwei Chen ◽  
...  
Keyword(s):  
B Cells ◽  
Apolipoprotein E ◽  
Colorimetric Assay ◽  
In Vivo Studies ◽  
Regulatory Subunit ◽  
Community Control ◽  
Mimetic Peptides ◽  
Therapeutic Peptides

Abstract Background and Significance : Even though we have treatments for CLL, it remains an incurable leuke mia. We need new and better treatments for this disease. The Akt kinase is usually constitutively acti vated (phosphorylated) in CLL, and it acts to maintain CLL cell viability. Chromosome deletion at 11q22–23 is frequently seen in CLL, and this cytogenetic abnormality portends a bad prognosis. The PPP2R1B gene that encodes the Ab constant regulatory subunit of the tumor suppressor protein phos phatase 2a (PP2a) is within the deleted segment in CLL patients with deleted 11q22–23. The resulting underexpression noted in those with deleted 11q22–23 leads to decreased PP2a activity in CLL cells. PP2a is important in deactivation of Akt, the mitogen activated protein kinases (MAPK) p38, JNK, ERK, and nuclear factor kB (through IkK). We have developed apolipoprotein E-mimetic therapeutic peptides that potently decrease phosphorylation of Akt, decrease TNF and nitric oxide (NO) and NO synthase (NOS) expression, and display anti-inflammatory activity in vitro and in vivo. NOS is overexpressed in CLL, and its product NO inhibits CLL cell apoptosis. Methods : Patients were from the V.A. and Duke University Medical Centers, and normal controls were from the community. Control normal PBMC were isolated by ficoll-Hypaque centrifugation, and CD19+ CLL or normal B cells were purified using negative selection with antibodies. We determined cytotoxicity using the MTS colorimetric assay. The apoE-mimetic peptides were prepared by chemical synthesis. Results : The apoE-mimetic COG compounds are peptides of 10 to 34 amino acids derived from the ligand-binding region of the apolipoprotein E holoprotein. Samples from 6 early stage CLL patients and 11 normal individuals were examined. Five of 6 patients were Rai stage 0 at presentation, and one was stage 1. They had been followed 5.6 yr (median; range 1.9–10.6 yr). Five of 6 were CD38 negative, and 2 of 6 were Zap-70 positive. Of 5analyzed, all had mutated IgVH gene. Five of 6 patients had not been treated. Of 6 peptides examined, all displayed some cytotoxicity for CLL cells in vitro. Peptide COG 112 was the most potent, while the control peptide with an inverted sequence (COG 056) had very little or no activity (Table). CLL PBMC Agent ED50 (nM) ED50 range (n) ED50 (nM) ED50 range (n) COG 112 (active) 215 64 to 351 (6) 5,150 1,100 to >12,500 (6) COG 056 (control) 13,546 2771 to 20,418 (6) >25,000 20,470 to >25,500 (6) COG 112 induced cell death in a dose-dependent fashion in all patients’ samples.The ED50 of COG 112 for normal B cells was very high (> 24,400 nM). COG 112 was approximatel 24 to 116 fold more potent for killing of CLL cells compared to normal PBMC or purified B cells. In vivo studies in normal mice using COG 112 revealed no toxicity even with doses of 100 mg/kg. Conclusions : ApoE mimetic peptides kill CLL cells in vitro with high efficacy and potency (ED50s in the low nanomolar range). The cytotoxicity is very specific for CLL cells compared to normal PBMC and B cells (24 to 116 fold more potent for CLL cells). Preliminary studies show that the peptide is nontoxic in vivo in normal mice. In vivo trials with apoE peptides in patients with CLL should help determine the toxicity and efficacy in patients.

Downregulation of Microglial Activation by Apolipoprotein E and ApoE-Mimetic Peptides

2001 ◽  
Vol 167 (1) ◽  
pp. 74-85 ◽  
Author(s):  
D.T. Laskowitz ◽  
A.D. Thekdi ◽  
S.D. Thekdi ◽  
S.K.D. Han ◽  
J.K. Myers ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Microglial Activation ◽  
Mimetic Peptides

scholarly journals Effects of an Aβ-antibody fragment on Aβ aggregation and astrocytic uptake are modulated by apolipoprotein E and J mimetic peptides

PLoS ONE ◽  
2017 ◽  
Vol 12 (11) ◽  
pp. e0188191 ◽  
Author(s):  
Laia Montoliu-Gaya ◽  
Sandra D. Mulder ◽  
Robert Veerhuis ◽  
Sandra Villegas
Keyword(s):  
Apolipoprotein E ◽  
Antibody Fragment ◽  
Mimetic Peptides ◽  
Aβ Aggregation
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