Effects of sex hormones on Alzheimer's disease-associated β-amyloid oligomer formation in vitro

2011 ◽  
Vol 228 (2) ◽  
pp. 298-302 ◽  
Author(s):  
Akiyoshi Morinaga ◽  
Kenjiro Ono ◽  
Junichi Takasaki ◽  
Tokuhei Ikeda ◽  
Mie Hirohata ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Hormones ◽  
Oligomer Formation ◽  
Β Amyloid ◽  
Amyloid Oligomer

Synthesis of a Novel Curcumin Derivative as a Potential Imaging Probe in Alzheimer’s Disease Imaging

2019 ◽  
Vol 16 (8) ◽  
pp. 723-731 ◽  
Author(s):  
Alexander Sturzu ◽  
Sumbla Sheikh ◽  
Hubert Kalbacher ◽  
Thomas Nägele ◽  
Christopher Weidenmaier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Flow Cytometry ◽  
Transgenic Mice ◽  
Ex Vivo ◽  
Amyloid Plaques ◽  
Laser Scanning Microscopy ◽  
Β Amyloid ◽  
Curcumin Derivative

Background: Curcumin has been of interest in the field of Alzheimer’s disease. Early studies on transgenic mice showed promising results in the reduction of amyloid plaques.However, curcumin is very poorly soluble in aqueous solutions and not easily accessible to coupling as it contains only phenolic groups as potential coupling sites. For these reasons only few imaging studies using curcumin bound as an ester were performed and curcumin is mainly used as nutritional supplement. Methods: In the present study we produced an aminoethyl ether derivative of curcumin using a nucleophilic substitution reaction. This is a small modification and should not impact the properties of curcumin while introducing an easily accessible reactive amino group. This novel compound could be used to couple curcumin to other molecules using the standard methods of peptide synthesis. We studied the aminoethyl-curcumin compound and a tripeptide carrying this aminoethyl-curcumin and the fluorescent dye fluorescein (FITC-curcumin) in vitro on cell culture using confocal laser scanning microscopy and flow cytometry. Then these two substances were tested ex vivo on brain sections prepared from transgenic mice depicting Alzheimer-like β-amyloid plaques. Results: In the in vitro CLSM microscopy and flow cytometry experiments we found dot-like unspecific uptake and only slight cytotoxicity correlating with this uptake. As these measurements were optimized for the use of fluorescein as dye we found that the curcumin at 488nm fluorescence excitation was not strong enough to use it as a fluorescence marker in these applications. In the ex vivo sections CLSM experiments both the aminoethyl-curcumin and the FITC-curcumin peptide bound specifically to β- amyloid plaques. Conclusion: In conclusion we successfully produced a novel curcumin derivative which could easily be coupled to other imaging or therapeutic molecules as a sensor for amyloid plaques.

scholarly journals Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s Disease: In Vitro and in Vivo Studies

2013 ◽  
Vol 4 (6) ◽  
pp. 973-982 ◽  
Author(s):  
Alaa H. Abuznait ◽  
Hisham Qosa ◽  
Belnaser A. Busnena ◽  
Khalid A. El Sayed ◽  
Amal Kaddoumi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Olive Oil ◽  
In Vivo Studies ◽  
Β Amyloid

scholarly journals Therapeutic Potential Of Multifunctional Derivatives Of Cholinesterase Inhibitors

2020 ◽  
Vol 19 ◽  
Author(s):  
Maja Przybyłowska ◽  
Krystyna Dzierzbicka ◽  
Szymon Kowalski ◽  
Klaudia Chmielewska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Amyloid Plaque ◽  
Β Amyloid ◽  
Derivatives Of ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

: The aim of this work is review of tacrine analogues from the last three years, which were not included in the latest review work, donepezil and galantamine hybrids from 2015 and rivastigmine derivatives from 2014. In this account we summarize the efforts toward the development and characterization of non-toxic inhibitors of cholinesterases based on mentioned drugs with various interesting additional properties such as antioxidant, decreasing β-amyloid plaque aggregation, nitric oxide production, pro-inflammatory cytokines release, monoamine oxidase-B activity, cytotoxicity and oxidative stress in vitro and in animal model that classify these hybrids as potential multifunctional therapeutic agents for Alzheimer’s disease. Moreover, herein, we have described the cholinergic hypothesis, mechanisms of neurodegeneration and current pharmacotherapy of Alzheimer’s disease which is based on the restoration of cholinergic function through blocking enzymes that break down acetylcholine.

P1-174: Early detection of β-amyloid aggregation in in vivo and in vitro models of Alzheimer's disease

2010 ◽  
Vol 6 ◽  
pp. S224-S224 ◽  
Author(s):  
Louise A. Scrocchi ◽  
Elizabeth Karaskov ◽  
Vivian Lee ◽  
Hui Chen ◽  
Melissa Osborne ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Detection ◽  
In Vitro Models ◽  
Amyloid Aggregation ◽  
Β Amyloid

scholarly journals Characterization of a Novel Mouse Model of Alzheimer’s Disease—Amyloid Pathology and Unique β-Amyloid Oligomer Profile

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0126317 ◽  
Author(s):  
Peng Liu ◽  
Jennifer B. Paulson ◽  
Colleen L. Forster ◽  
Samantha L. Shapiro ◽  
Karen H. Ashe ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Pathology ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid ◽  
Amyloid Oligomer

scholarly journals Apolipoprotein E forms stable complexes with recombinant Alzheimer's disease β-amyloid precursor protein

1997 ◽  
Vol 325 (1) ◽  
pp. 169-175 ◽  
Author(s):  
Cristina HAAS ◽  
Pilar CAZORLA ◽  
Carlos DE MIGUEL ◽  
Fernando VALDIVIESO ◽  
Jesús VÁZQUEZ
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Senile Plaques ◽  
Precursor Protein ◽  
Amyloid Peptide ◽  
Reducing Conditions ◽  
Β Amyloid

Apolipoprotein E (apoE), a protein genetically linked to the incidence of Alzheimer's disease, forms SDS-stable complexes in vitro with β-amyloid peptide (Aβ), the primary component of senile plaques. In the present study, we investigated whether apoE was able to bind full-length Aβ precursor protein (APP). Using a maltose-binding-protein–APP fusion protein and human very-low-density lipoprotein (VLDL), we detected an interaction of apoE with APP that was inhibited by Aβ or anti-apoE antibody. Saturation-binding experiments indicated a single binding equilibrium with an apparent 1:1 stoichiometry and a dissociation constant of 15 nM. An interaction was also observed using apoE from cerebrospinal fluid or delipidated VLDL, as well as recombinant apoE. APP·apoE complexes were SDS-stable, and their formation was not inhibited by reducing conditions; however, they were dissociated by SDS under reducing conditions. ApoE·APP complexes formed high-molecular-mass aggregates, and competition experiments suggested that amino acids 14–23 of Aβ are responsible for complex-formation. Finally, no differences were found when studying the interaction of APP with apoE3 or apoE4. Taken together, our results demonstrate that apoE may form stable complexes with the Aβ moiety of APP with characteristics similar to those of complexes formed with isolated Aβ, and suggest the intriguing possibility that apoE–APP interactions may be pathologically relevant in vivo.

RANDOMIZED, PLACEBO CONTROLLED TRIAL OF NPT088, A PHAGE-DERIVED, AMYLOID-TARGETED TREATMENT FOR ALZHEIMER’S DISEASE

2019 ◽  
pp. 1-4
Author(s):  
D. Michelson ◽  
M. Grundman ◽  
K. Magnuson ◽  
R. Fisher ◽  
J.M. Levenson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Controlled Trial ◽  
Positron Emission Tomography Imaging ◽  
Amyloid Plaque ◽  
Disease Symptoms ◽  
Positron Emission ◽  
Infusion Reactions ◽  
Β Amyloid

The engineered fusion protein NPT088 targets amyloid in vitro and in animal models of Alzheimer’s disease. Previous studies showed that NPT088 treatment reduced β-amyloid plaque and tau aggregate loads in mouse disease models. Here, we present the results from an initial clinical study of NPT088 in patients with mild to moderate Alzheimer’s disease. Patients were treated with 4 dose levels of NPT088 for 6 months to evaluate its safety and tolerability. Exploratory measurements included measurement of change in β-amyloid plaque and tau burden utilizing Positron Emission Tomography imaging as well as measures of Alzheimer’s disease symptoms. At endpoint NPT088 was generally safe and well-tolerated with the most prominent finding being infusion reactions in a minority of patients. No effect of NPT088 on brain plaques, tau aggregates or Alzheimer’s disease symptoms was observed.

scholarly journals Centella asiaticaExtract Improves Behavioral Deficits in a Mouse Model of Alzheimer's Disease: Investigation of a Possible Mechanism of Action

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Amala Soumyanath ◽  
Yong-Ping Zhong ◽  
Edward Henson ◽  
Teri Wadsworth ◽  
James Bishop ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Water Extract ◽  
Glutamate Toxicity ◽  
Tg2576 Mouse ◽  
Asiatic Acid ◽  
Human Neuroblastoma ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid

Centella asiatica(CA), commonly named gotu kola, is an Ayurvedic herb used to enhance memory and nerve function. To investigate the potential use of CA in Alzheimer's disease (AD), we examined the effects of a water extract of CA (GKW) in the Tg2576 mouse, a murine model of AD with high β-amyloid burden. Orally administered GKW attenuated β-amyloid-associated behavioral abnormalities in these mice.In vitro, GKW protected SH-SY5Y cells and MC65 human neuroblastoma cells from toxicity induced by exogenously added and endogenously generated β-amyloid, respectively. GKW prevented intracellular β-amyloid aggregate formation in MC65 cells. GKW did not show anticholinesterase activity or protect neurons from oxidative damage and glutamate toxicity, mechanisms of current AD therapies. GKW is rich in phenolic compounds and does not contain asiatic acid, a known CA neuroprotective triterpene. CA thus offers a unique therapeutic mechanism and novel active compounds of potential relevance to the treatment of AD.

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