The Ups and Downs of BACE1: Walking a Fine Line between Neurocognitive and Other Psychiatric Symptoms of Alzheimer’s Disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F21%3A43920263" target="_blank" >RIV/00023752:_____/21:43920263 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/21:43920309

Výsledek na webu

<a href="https://journals.sagepub.com/doi/10.1177/1073858420940943" target="_blank" >https://journals.sagepub.com/doi/10.1177/1073858420940943</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1177/1073858420940943" target="_blank" >10.1177/1073858420940943</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The Ups and Downs of BACE1: Walking a Fine Line between Neurocognitive and Other Psychiatric Symptoms of Alzheimer’s Disease

Popis výsledku v původním jazyce

Although neurocognitive deficit is the best-recognized indicator of Alzheimer’s disease (AD), psychotic and other noncognitive symptoms are the prime cause of institutionalization. BACE1 is the rate-limiting enzyme in the production of Aβ of AD, and one of the promising therapeutic targets in countering the cognitive decline and amyloid pathology. Changes in BACE1 activity have also emerged to cause significant noncognitive neuropsychiatric symptoms and impairments of circadian rhythms, as evident from clinical trials and reports in transgenic models. In this study, we consider key characteristics of BACE1 with its contribution to neurocognitive impairments and other psychiatric symptoms of AD. We argue that a growing list of noncognitive mental impairments related to pharmacological modulation of BACE1 might present a major obstacle in clinical translation of emerging therapeutic leads targeting this protease. The adverse effects of BACE1 inhibition on mental health call for a revision of treatment strategies that assume indiscriminate inhibition of this key protease, and stress the need for further mechanistic and translational studies.

Název v anglickém jazyce

The Ups and Downs of BACE1: Walking a Fine Line between Neurocognitive and Other Psychiatric Symptoms of Alzheimer’s Disease

Popis výsledku anglicky

Although neurocognitive deficit is the best-recognized indicator of Alzheimer’s disease (AD), psychotic and other noncognitive symptoms are the prime cause of institutionalization. BACE1 is the rate-limiting enzyme in the production of Aβ of AD, and one of the promising therapeutic targets in countering the cognitive decline and amyloid pathology. Changes in BACE1 activity have also emerged to cause significant noncognitive neuropsychiatric symptoms and impairments of circadian rhythms, as evident from clinical trials and reports in transgenic models. In this study, we consider key characteristics of BACE1 with its contribution to neurocognitive impairments and other psychiatric symptoms of AD. We argue that a growing list of noncognitive mental impairments related to pharmacological modulation of BACE1 might present a major obstacle in clinical translation of emerging therapeutic leads targeting this protease. The adverse effects of BACE1 inhibition on mental health call for a revision of treatment strategies that assume indiscriminate inhibition of this key protease, and stress the need for further mechanistic and translational studies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LO1611" target="_blank" >LO1611: Udržitelnost pro Národní ústav duševního zdraví</a><br>

Návaznosti

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

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Neuroscientist

ISSN

1073-8584

e-ISSN

—

Svazek periodika

27

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

222-234

Kód UT WoS článku

000552714900001

EID výsledku v databázi Scopus

2-s2.0-85088434964