Beta-secretase 2

Beta-secretase 2 (BACE2) is an enzyme that in humans is encoded by the BACE2 gene. It is a member of the aspartyl protease family, which plays a significant role in the protein processing mechanisms of neurodegenerative diseases, including Alzheimer's disease. Unlike its close homolog, BACE1, which has been extensively studied for its role in producing beta-amyloid peptides by cleaving amyloid precursor protein (APP), BACE2 is involved in alternative cleavage pathways and has been suggested to have protective roles against the accumulation of amyloid plaques.

Function

BACE2 acts by cleaving proteins at specific peptide bonds, a critical process in the formation, maturation, and degradation of many bioactive peptides and proteins. In the context of Alzheimer's disease, while BACE1's activity is associated with the production of neurotoxic beta-amyloid peptides, BACE2 has been shown to cleave APP at a different site, potentially reducing the formation of these harmful peptides. This has led to a growing interest in BACE2 as a potential therapeutic target for Alzheimer's disease, as enhancing its activity could offer a novel approach to reducing amyloid burden.

Genetics

The BACE2 gene is located on chromosome 21, close to the Down syndrome critical region. This positioning has led to investigations into the role of BACE2 in Down syndrome, as individuals with this condition have an extra copy of chromosome 21 and are at increased risk of developing Alzheimer's disease at an earlier age. The gene's location and its potential protective effects against amyloid accumulation make it a subject of interest in both conditions.

Clinical Significance

Research into BACE2 has expanded beyond its implications in neurodegenerative diseases. Studies have suggested roles in diabetes due to its expression in the pancreas and involvement in the regulation of insulin secretion. Furthermore, mutations in the BACE2 gene have been explored for their potential links to susceptibility to various conditions, including Alzheimer's disease and diabetes.

Potential Therapeutic Target

Given its distinct cleavage activity on APP and potential protective effects against Alzheimer's disease, BACE2 has been considered a promising therapeutic target. Strategies to enhance BACE2 activity or mimic its action on APP could offer new avenues for treatment, aiming to reduce the pathological accumulation of beta-amyloid peptides. However, the development of such therapies requires a deeper understanding of BACE2's functions, substrates, and regulation.

See Also

• Amyloid precursor protein
• Beta-secretase 1
• Alzheimer's disease
• Down syndrome
• Aspartyl protease