Multitarget tacrine hybrids with neuroprotective properties to confront Alzheimer's disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F17%3A43919250" target="_blank" >RIV/00023752:_____/17:43919250 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/17:43889387 RIV/00179906:_____/17:10338063

Výsledek na webu

<a href="http://www.eurekaselect.com/145857/article" target="_blank" >http://www.eurekaselect.com/145857/article</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1568026605666160927152728" target="_blank" >10.2174/1568026605666160927152728</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Multitarget tacrine hybrids with neuroprotective properties to confront Alzheimer's disease

Popis výsledku v původním jazyce

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder. Several hallmarks such as β-amyloid (Aβ) aggregation underlying amyloid plaque formation, τ-hyperphosphorylation leading to production of neurofibrillary tangles, and decline in the number of cholinergic neurons appear to be fundamental in the pathophysiology of the disease. Other evidence points also to the involvement of oxidative stress, biometal dyshomeostasis, inflammation, and cell cycle regulatory failure. Taking into account such premises, many attractive targets for the development of anti-AD drugs have emerged. Specifically, the multifactorial nature of AD calls for multi-target-directed ligands (MTDLs) which can be beneficial by providing interactions with multiple targets. Tacrine (THA), the first clinically effective acetylcholinesterase inhibitor, was approved for the treatment of mild to moderate AD. Unfortunately, frequent adverse effects including peripheral cholinergic effects and hepatotoxicity limited its therapeutic potential. Based on the numerous biological systems involved in AD progression, this review covers THA-incorporated hybrids possessing a neuroprotective profile. In particular, it focuses on THA hybrids capable of scavenging reactive oxygen species (ROS), and derivatives which reduce the formation of Aβ-plaques either directly by confronting the Aβ1-42 selfaggregation process or indirectly by inhibiting the BACE-1 enzyme or AChE-induced Aβ1-40 aggregation. Particular interest is also addressed to THA hybrids with suppressed hepatotoxicity.

Název v anglickém jazyce

Multitarget tacrine hybrids with neuroprotective properties to confront Alzheimer's disease

Popis výsledku anglicky

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder. Several hallmarks such as β-amyloid (Aβ) aggregation underlying amyloid plaque formation, τ-hyperphosphorylation leading to production of neurofibrillary tangles, and decline in the number of cholinergic neurons appear to be fundamental in the pathophysiology of the disease. Other evidence points also to the involvement of oxidative stress, biometal dyshomeostasis, inflammation, and cell cycle regulatory failure. Taking into account such premises, many attractive targets for the development of anti-AD drugs have emerged. Specifically, the multifactorial nature of AD calls for multi-target-directed ligands (MTDLs) which can be beneficial by providing interactions with multiple targets. Tacrine (THA), the first clinically effective acetylcholinesterase inhibitor, was approved for the treatment of mild to moderate AD. Unfortunately, frequent adverse effects including peripheral cholinergic effects and hepatotoxicity limited its therapeutic potential. Based on the numerous biological systems involved in AD progression, this review covers THA-incorporated hybrids possessing a neuroprotective profile. In particular, it focuses on THA hybrids capable of scavenging reactive oxygen species (ROS), and derivatives which reduce the formation of Aβ-plaques either directly by confronting the Aβ1-42 selfaggregation process or indirectly by inhibiting the BACE-1 enzyme or AChE-induced Aβ1-40 aggregation. Particular interest is also addressed to THA hybrids with suppressed hepatotoxicity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

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

Current Topics in Medicinal Chemistry

ISSN

1568-0266

e-ISSN

—

Svazek periodika

17

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

21

Strana od-do

1006-1026

Kód UT WoS článku

000394571200004

EID výsledku v databázi Scopus

2-s2.0-85013797993