Alzheimer's disease drugs- in vitro comparison of cholinesterase inhibition and beta-amyloid modulation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F17%3A43915459" target="_blank" >RIV/00023752:_____/17:43915459 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/17:43875762 RIV/62690094:18470/17:50013381 RIV/00216208:11160/17:10360913 RIV/00179906:_____/17:10360913

Výsledek na webu

<a href="http://www.eurekaselect.com/148776/article" target="_blank" >http://www.eurekaselect.com/148776/article</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1570180814666161228143846" target="_blank" >10.2174/1570180814666161228143846</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Alzheimer's disease drugs- in vitro comparison of cholinesterase inhibition and beta-amyloid modulation

Popis výsledku v původním jazyce

Background: Alzheimer’s disease is progressive neurodegenerative disease incidence of which has been steadily growing for past decades. Etiology of Alzheimer’s disease consists of multiple micro and macroscopic changes and to this day is not satisfactorily understood. Conventional therapy is based on inhibition of acetylcholinesterase of Alzheimer’s disease is connected with considerable worldwide expenses. Objective: Six clinically used cholinesterase inhibitors (donepezil, physostigmine, galanthamine, huperzine A, rivastigmine and tacrine) and memantine were compared according to their cholinesterase inhibitory properties. Additionally, the ability of tested compounds to directly inhibit protein aggregation as well as the capability to promote the protein amyloid fibrils depolymerization was determined. Method: Adopted colorimetric assay according to Ellman was used to evaluate the inhibition aktivity against cholinesterases. The ability of compounds to influence agregation inhibition and depolymerization activity was measured by means of thioflavin fluorescence assay. Results: Huperzine A was found to be the most potent, highly selective acetylcholinesterase inhibitor. Tacrine and physostigmine were the most potent butyrylcholinesterase inhibitors. Several inhibitors showed some weak potency to affect protein fibrils aggregation or depolymerization. Namely rivastigmine and galanthamine showed some effect on protein polymerization and depolymerization. Conclusion: Data provided by experiments suggest that clinically used and standard cholinesterase inhibitors influence the protein superstructures however the effect is weak. The need for novel structures of cholinesterase inhibitors with sufficient protein aggregation inhibition and/or depolymerization is evident.

Název v anglickém jazyce

Alzheimer's disease drugs- in vitro comparison of cholinesterase inhibition and beta-amyloid modulation

Popis výsledku anglicky

Background: Alzheimer’s disease is progressive neurodegenerative disease incidence of which has been steadily growing for past decades. Etiology of Alzheimer’s disease consists of multiple micro and macroscopic changes and to this day is not satisfactorily understood. Conventional therapy is based on inhibition of acetylcholinesterase of Alzheimer’s disease is connected with considerable worldwide expenses. Objective: Six clinically used cholinesterase inhibitors (donepezil, physostigmine, galanthamine, huperzine A, rivastigmine and tacrine) and memantine were compared according to their cholinesterase inhibitory properties. Additionally, the ability of tested compounds to directly inhibit protein aggregation as well as the capability to promote the protein amyloid fibrils depolymerization was determined. Method: Adopted colorimetric assay according to Ellman was used to evaluate the inhibition aktivity against cholinesterases. The ability of compounds to influence agregation inhibition and depolymerization activity was measured by means of thioflavin fluorescence assay. Results: Huperzine A was found to be the most potent, highly selective acetylcholinesterase inhibitor. Tacrine and physostigmine were the most potent butyrylcholinesterase inhibitors. Several inhibitors showed some weak potency to affect protein fibrils aggregation or depolymerization. Namely rivastigmine and galanthamine showed some effect on protein polymerization and depolymerization. Conclusion: Data provided by experiments suggest that clinically used and standard cholinesterase inhibitors influence the protein superstructures however the effect is weak. The need for novel structures of cholinesterase inhibitors with sufficient protein aggregation inhibition and/or depolymerization is evident.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Letters in Drug Design &amp; Discovery

ISSN

1570-1808

e-ISSN

—

Svazek periodika

14

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

8

Strana od-do

743-750

Kód UT WoS článku

000404984700013

EID výsledku v databázi Scopus

2-s2.0-85022195251