Navigating the Maze of Alzheimer's disease by exploring BACE1: Discovery, current scenario, and future prospects.
Ageing Res Rev
; 98: 102342, 2024 07.
Article
em En
| MEDLINE
| ID: mdl-38762102
ABSTRACT
Alzheimer's disease (AD) is a chronic neurological condition that has become a leading cause of cognitive decline in elder individuals. Hardly any effective medication has been developed to halt the progression of AD due to the disease's complexity. Several theories have been put forward to clarify the mechanisms underlying AD etiology. The identification of amyloid plaques as a hallmark of AD has sparked the development of numerous drugs targeting the players involved in the amyloidogenic pathway, such as the ß-site of amyloid precursor protein cleavage enzyme 1 (BACE1) blockers. Over the last ten years, preclinical and early experimental research has led several pharmaceutical companies to prioritize producing BACE1 inhibitors. Despite all these efforts, earlier discovered inhibitors were discontinued in consideration of another second-generation small molecules and recent BACE1 antagonists failed in the final stages of clinical trials because of the complications associated either with toxicity or effectiveness. In addition to discussing the difficulties associated with development of BACE1 inhibitors, this review aims to provide an overview of BACE1 and offer perspectives on the causes behind the failure of five recent BACE1 inhibitors, that would be beneficial for choosing effective treatment approaches in the future.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Aspártico Endopeptidases
/
Secretases da Proteína Precursora do Amiloide
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Doença de Alzheimer
Limite:
Animals
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Humans
Idioma:
En
Revista:
Ageing Res Rev
Assunto da revista:
GERIATRIA
Ano de publicação:
2024
Tipo de documento:
Article