World Alzheimer Conference 2000: Nearing Home BACE?

Series - World Alzheimer Conference 2000:

There were a number of oral and poster presentations relating to BACE biology (abstracts 313, 504, 540, 1013, 1269 and 1272). As with the original descriptions of BACE, the reports presented at this meeting were in broad agreement. Undoubtedly the most noteworthy presentation was by Martin Citron, but for convenience I have synthesized the findings of a number groups and listed them below.

  1. BACE is expressed on the cell surface, but undergoes N-terminal processing and glycosylation in the Golgi and accumulates in endosomes.
  2. Active site-directed mutagenesis (at Asp 93 or Asp289) did not alter pro-peptide cleavage of BACE indicating that this is not an endoproteolytic event.
  3. Pro-peptide cleavage appears to be mediated by Furin as active BACE is not produced in Furin-deficient cells, but can be induced by transfection of such cells with Furin.
  4. BACE is N-glycosylated at three of four possible sites.
  5. BACE contains three intramolecular disulfide bonds between the Cys pairs: 330-380, 278-443 and 216-420. Disruption of any of the three disulfides results in a loss of enzymatic activity indicating that all three bridges play a critical role in maintaining the required 3D conformation.—Dominic Walsh

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