BACE

Beta-secretase 1 (BACE1), also known as beta-site APP cleaving enzyme 1, is an enzyme that in humans is encoded by the BACE1 gene on chromosome 11. BACE1 is a protease that plays a critical role in the formation of amyloid beta, a peptide of 36–43 amino acids that is critical in the formation of amyloid plaques found in the brains of Alzheimer's disease patients. The enzyme acts by cleaving amyloid precursor protein (APP) at the beta site, which is one of the first steps in the production of amyloid beta. Due to its role in the generation of amyloid beta, BACE1 is a prime target for therapeutic intervention in Alzheimer's disease.

Function

BACE1 is an aspartic-acid protease important in the pathogenesis of Alzheimer's disease, and abnormal levels of this enzyme may also be associated with other neurological conditions. The enzyme specifically cleaves the amyloid precursor protein, leading to the accumulation of amyloid beta peptides in the brain, a hallmark of Alzheimer's pathology. BACE1 is considered a membrane-bound enzyme and is found in various tissues but is particularly abundant in the brain.

Clinical Significance

The critical role of BACE1 in the formation of neurotoxic amyloid beta peptides makes it a significant target for Alzheimer's disease therapy. Inhibitors of BACE1 are being researched and developed as potential therapeutic agents to reduce or inhibit the production of amyloid beta, thereby potentially slowing the progression of Alzheimer's disease. However, the development of BACE1 inhibitors has been challenging due to the need for specificity and the ability to cross the blood-brain barrier.

Genetics

The BACE1 gene is located on the long (q) arm of chromosome 11 at position 15.3, from base pair 119,148,345 to base pair 119,213,067. Mutations in this gene or variations in its expression can influence the activity of the enzyme and have been studied in the context of Alzheimer's disease risk.

Research

Research into BACE1 includes the study of its structure, function, and inhibitors that can effectively reduce amyloid beta production without significant side effects. Studies also focus on understanding the regulation of BACE1 expression and its role in the pathogenesis of Alzheimer's disease and other neurological disorders. The development of animal models that overexpress or lack BACE1 is crucial for testing the effects of potential therapeutic interventions.

See Also

• Amyloid precursor protein
• Alzheimer's disease
• Protease
• Amyloid plaques