Is It the Twilight of BACEI Inhibitors?

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F21%3A50018771" target="_blank" >RIV/62690094:18470/21:50018771 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/21:00556865 RIV/00179906:_____/21:10426434

Výsledek na webu

<a href="https://www.eurekaselect.net/article/106293" target="_blank" >https://www.eurekaselect.net/article/106293</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1570159X18666200503023323" target="_blank" >10.2174/1570159X18666200503023323</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Is It the Twilight of BACEI Inhibitors?

Popis výsledku v původním jazyce

beta-secretase (BACE1) has been regarded as a prime target for the development of amyloid beta (A beta) lowering drugs in the therapy of Alzheimer&apos;s disease (A beta). Although the enzyme was discovered in 1991 and helped to formulate the AD hypothesis as one of the very important features of A beta etiopathogenesis, progress in A beta treatment utilizing BACE1 inhibitors has remained limited. Moreover, in the last years, major pharmaceutical companies have discontinued clinical trials of five BACE1 inhibitors that had been strongly perceived as prospective. In our review, the A beta hypothesis, the enzyme, its functions, and selected substrates are described. BACE1 inhibitors are classified into four generations. Those that underwent clinical trials displayed adverse effects, including weight loss, skin rashes, worsening of neuropsychiatric symptoms, etc. Some inhibitors could not establish a statistically significant risk-benefit ratio, or even scored worse than placebo. We still believe that drugs targeting BACE1 may still hide some potential, but a different approach to BACE1 inhibition or a shift of focus to modulation of its trafficking and/or post-translational modification should now be followed.

Název v anglickém jazyce

Is It the Twilight of BACEI Inhibitors?

Popis výsledku anglicky

beta-secretase (BACE1) has been regarded as a prime target for the development of amyloid beta (A beta) lowering drugs in the therapy of Alzheimer&apos;s disease (A beta). Although the enzyme was discovered in 1991 and helped to formulate the AD hypothesis as one of the very important features of A beta etiopathogenesis, progress in A beta treatment utilizing BACE1 inhibitors has remained limited. Moreover, in the last years, major pharmaceutical companies have discontinued clinical trials of five BACE1 inhibitors that had been strongly perceived as prospective. In our review, the A beta hypothesis, the enzyme, its functions, and selected substrates are described. BACE1 inhibitors are classified into four generations. Those that underwent clinical trials displayed adverse effects, including weight loss, skin rashes, worsening of neuropsychiatric symptoms, etc. Some inhibitors could not establish a statistically significant risk-benefit ratio, or even scored worse than placebo. We still believe that drugs targeting BACE1 may still hide some potential, but a different approach to BACE1 inhibition or a shift of focus to modulation of its trafficking and/or post-translational modification should now be followed.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

CURRENT NEUROPHARMACOLOGY

ISSN

1570-159X

e-ISSN

—

Svazek periodika

19

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

17

Strana od-do

61-77

Kód UT WoS článku

000625073600005

EID výsledku v databázi Scopus

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