Function, regulation and therapeutic properties of beta-secretase (BACE1)
Semin Cell Dev Biol. 2009 Apr;20(2):175-82. Epub 2009 Jan 20.
| Authors/Editors: |
Willem M Lammich S Haass C |
|---|---|
| Publication Date: | 2009 |
| Type of Publication: | Journal Article |
beta-Secretase (beta-site amyloid precursor protein cleaving enzyme 1; BACE1) has
been identified as the rate limiting enzyme for amyloid-beta-peptide (Abeta)
production. Abeta is the major component of amyloid plaques and vascular deposits
in Alzheimer's disease (AD) brains and believed to initiate the deadly amyloid
cascade. BACE1 is the principle beta-secretase, since its knock-out completely
prevents Abeta generation. BACE1 is likely to process a number of different
substrates and consequently several independent physiological functions may be
exerted by BACE1. Currently the function of BACE1 in myelination is best
understood. BACE1 cleaves and activates Neuregulin-1 and is thus directly
involved in myelination of the peripheral nervous system during early postnatal
development. However, additional physiological functions specifically within the
central nervous system are so far less understood. BACE1 is upregulated in at
least some AD brains. Multiple cellular mechanisms for BACE1 regulation are known
including post-transcriptional regulation via its 5'-untranslated region,
microRNA and non-coding anti-sense RNA. BACE1 is a primary target for Abeta
lowering therapies, however the development of high affinity bio-available
inhibitors has been a major challenge so far.
