Secretases in Alzheimer's disease: Novel insights into proteolysis of APP and TREM2
| Autor: | Harald Steiner, Sarah K. Tschirner, Stefan F. Lichtenthaler |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Proteases
therapeutic use [Membrane Glycoproteins] ADAM10 Proteolysis genetics [Amyloid Precursor Protein Secretases] metabolism [Amyloid beta-Peptides] therapeutic use [Amyloid beta-Peptides] therapeutic use [ADAM10 Protein] ADAM10 Protein Amyloid beta-Protein Precursor Alzheimer Disease mental disorders metabolism [Amyloid beta-Protein Precursor] Amyloid precursor protein Disintegrin medicine Aspartic Acid Endopeptidases Humans therapeutic use [Receptors Immunologic] ddc:610 Receptors Immunologic therapeutic use [Amyloid beta-Protein Precursor] Metalloproteinase Amyloid beta-Peptides Membrane Glycoproteins biology medicine.diagnostic_test TREM2 General Neuroscience therapeutic use [Amyloid Precursor Protein Secretases] metabolism [Receptors Immunologic] metabolism [Aspartic Acid Endopeptidases] metabolism [Amyloid Precursor Protein Secretases] genetics [Amyloid beta-Protein Precursor] genetics [Aspartic Acid Endopeptidases] therapeutic use [Aspartic Acid Endopeptidases] biology.protein metabolism [ADAM10 Protein] Amyloid Precursor Protein Secretases Neuroscience Amyloid precursor protein secretase metabolism [Membrane Glycoproteins] |
| Zdroj: | Current opinion in neurobiology 72, 101-110 (2022). doi:10.1016/j.conb.2021.09.003 |
| Popis: | 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 β-secretase β-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 β-secretase activity through transcriptional and post-translational mechanisms. Finally, new opportunities but also challenges are discussed for pharmacologically targeting β- and γ-secretase cleavage of APP and α-secretase cleavage of TREM2 with the aim to prevent or treat AD. |
| Databáze: | OpenAIRE |
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