. Expression of the Alzheimer protease BACE1 is suppressed via its 5'-untranslated region. EMBO Rep. 2004 Jun;5(6):620-5. PubMed.

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  1. This is an interesting paper that confirms and expands our published work (De Pietri Tonelli et al., 2004) on the strong repression that is exerted by the transcript leader of BACE-1 on its translation. This is a hot topic since modulation of the expression of BACE-1, the key enzyme in the production of β-amyloid, might have an important role in the pathogenesis of Alzheimer's disease. This confirmation is also important in order to shed some light in this issue, since another recent paper (Rogers et al., 2004) not only shows little inhibition but also proposes ribosomal shunting as the mechanism to overcome the translational hurdle in BACE-1 transcript leader. The different conclusions reached in Rogers' paper can be related to the cell lines they employed, but the question whether shunting may indeed occur in CNS cells remains open.

    References:

    . Translational regulation of BACE-1 expression in neuronal and non-neuronal cells. Nucleic Acids Res. 2004;32(5):1808-17. PubMed.

    . Differential utilization of upstream AUGs in the beta-secretase mRNA suggests that a shunting mechanism regulates translation. Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2794-9. PubMed.

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