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Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) (BACE1)

Target: BACE1
Molecular classification: Enzyme, Aspartic acid protease, Transmembrane protein

Overview

Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as Beta-secretase, is an aspartic acid protease. It plays a key role in the proteolytic processing of amyloid precursor protein (APP), and is a therapeutic target primarily for Alzheimer's disease, although many investigational inhibitors have faced safety or efficacy challenges.

Other names: Beta-secretase 1Membrane-associated aspartic protease 2Memapsin-2Aspartyl protease 2ASP2

Mechanism of action

Inhibition of enzymatic activity to prevent cleavage of APP and subsequent generation of amyloid-beta peptides[4]. Reduction of amyloid-beta plaque formation in Alzheimer's disease models.

Biological functions

Proteolytic processing of amyloid precursor protein (APP)Myelin sheath formation in peripheral nerve cellsProtein maturation and trimming[2][3][5]

Disease associations

Neurodegenerative disease (Alzheimer's disease)[4][5]

Safety considerations

Potential impairment of motor coordination due to effects on muscle spindles observed in animal models.Off-target effects related to inhibition of other physiological functions such as myelination and synaptic plasticity.

Interacting drugs

Multiple investigational BACE inhibitors (e.g., verubecestat, lanabecestat), though many have failed in clinical trials due to safety or efficacy issues. No currently approved drugs specifically targeting BACE1 are widely used.

Biomarkers

Amyloid-beta peptide levels in cerebrospinal fluid or plasma as potential biomarkers for patient selection or efficacy monitoring.Changes in APP processing products.

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