Secretases in Alzheimer's disease: Novel insights into proteolysis of APP and TREM2.
Curr Opin Neurobiol
; 72: 101-110, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34689040
Secretases are a group of proteases that are major drug targets considered for the prevention and treatment of Alzheimer's disease (AD). Secretases do not only process the AD-linked neuronal amyloid precursor protein (APP) but also the triggering receptor expressed on myeloid cells 2 (TREM2), thereby controlling microglial functions. This review highlights selected recent discoveries for the α-secretases a disintegrin and metalloprotease 10 (ADAM10) and a disintegrin and metalloprotease 17 (ADAM17), the ß-secretase ß-site APP cleaving enzyme 1 (BACE1) and γ-secretase and their link to AD. New genetic evidence strengthens the role of α-secretases in AD through cleavage of APP and TREM2. Novel proteins were linked to AD, which control α- and ß-secretase activity through transcriptional and post-translational mechanisms. Finally, new opportunities but also challenges are discussed for pharmacologically targeting ß- and γ-secretase cleavage of APP and α-secretase cleavage of TREM2 with the aim to prevent or treat AD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Secretases da Proteína Precursora do Amiloide
/
Doença de Alzheimer
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article