Gathering at the β-Secretase Corral

The October report in Science by Vassar and colleagues idetifying β-secretase, (see below) has now been followed up by three more reports this month identifying the BACE enzyme (or ASP2, as it has been termed by two of the groups)-one in the online journal Molecular and Cellular Neuroscience and two in Nature. Writing a News and Views article in Nature, Bart De Strooper and Gerhard Koenig welcome the new reports because the researchers took varied paths to get to the same point, helping to confirm the earlier reported results. For example, Yan and colleagues scanned the C elegans genome for aspartyl-protease-like gene products and then looked in the vertebrate genome for homologues of the proteases they had found. Sinha and colleagues took a classical protein fractionation approach to arrive at the same molecule, designing a transition state analogue that could "hook" or "freeze" the BACE molecule in the act of cleaving its substrate.—Hakon Heimer

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Primary Papers

  1. Hussain I, Powell D, Howlett DR, Tew DG, Meek TD, Chapman C, Gloger IS, Murphy KE, Southan CD, Ryan DM, Smith TS, Simmons DL, Walsh FS, Dingwall C, Christie G. Identification of a novel aspartic protease (Asp 2) as beta-secretase. Mol Cell Neurosci. 1999 Dec;14(6):419-27. PubMed.
  2. Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, Brashier JR, Stratman NC, Mathews WR, Buhl AE, Carter DB, Tomasselli AG, Parodi LA, Heinrikson RL, Gurney ME. Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature. 1999 Dec 2;402(6761):533-7. PubMed.
  3. Sinha S, Anderson JP, Barbour R, Basi GS, Caccavello R, Davis D, Doan M, Dovey HF, Frigon N, Hong J, Jacobson-Croak K, Jewett N, Keim P, Knops J, Lieberburg I, Power M, Tan H, Tatsuno G, Tung J, Schenk D, Seubert P, Suomensaari SM, Wang S, Walker D, Zhao J, McConlogue L, John V. Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature. 1999 Dec 2;402(6761):537-40. PubMed.
  4. De Strooper B, König G. Alzheimer's disease. A firm base for drug development. Nature. 1999 Dec 2;402(6761):471-2. PubMed.

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