Synonyms: beta-secretase 1, beta-Site amyloid beta A4 precursor protein-cleaving enzyme, memapsin-2 (membrane-associated aspartic protease 2), aspartyl protease 2 (ASP2), HSPC104


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BACE1 encodes a transmembrane aspartyl protease responsible for β-secretase processing of the amyloid precursor protein (APP). APP cleavage by BACE1 is the rate-limiting step in the generation of Aβ peptides, creating the C99 fragment that becomes a substrate for subsequent γ-secretase cleavage. BACE1 is active in the acidic environment of early endosomes and trans-Golgi compartments, where Aβ is generated.

Its role in Aβ generation has made BACE1 a target for therapy development, and rational drug design efforts accelerated when the crystal structure of BACE was solved. A handful of BACE inhibitors have come to clinical trial, though some failed in Phase 1 due to safety concerns. BACE inhibitors are being watched for potential off-target effects of BACE1 inhibition, as the protease cleaves several dozen substrates. The best-studied is the cell surface protein neuregulin 1, whose soluble cleavage product signals through the receptor Erb4 on glial cells to regulate myelination. In addition, BACE1 is known to play a role in neurite outgrowth and muscle spindle formation. BACE knockout mice have mild schizophrenia-like and cognitive phenotypes.

The physiological function of APP processing by BACE1 remains unclear. The homolog BACE2 differs from BACE1 in its expression pattern and substrate specificity, and appears not to contribute significantly to Aβ generation.


Other Citations

  1. amyloid precursor protein (APP)

Further Reading


  1. . The Membrane-Bound Aspartyl Protease BACE1: Molecular and Functional Properties in Alzheimer's Disease and Beyond. Front Physiol. 2012;3:8. PubMed.
  2. . β-Site APP-cleaving enzyme 1 trafficking and Alzheimer's disease pathogenesis. J Neurochem. 2012 Mar;120(6):869-80. PubMed.
  3. . Identification and biology of β-secretase. J Neurochem. 2012 Jan;120 Suppl 1:55-61. PubMed.
  4. . Regulation of β-site APP-cleaving enzyme 1 gene expression and its role in Alzheimer's disease. J Neurochem. 2012 Jan;120 Suppl 1:62-70. PubMed.
  5. . BACE1 as a potential biomarker for Alzheimer's disease. J Alzheimers Dis. 2011;24 Suppl 2:53-9. PubMed.
  6. . The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential. J Neurosci. 2009 Oct 14;29(41):12787-94. PubMed.