Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 5 June 2012
Vol. 5, Issue 227, p. ec160
[DOI: 10.1126/scisignal.2003278]


Biochemistry Insights into Amyloidogenesis

Valda K. Vinson

Science, AAAS, Washington, DC 20005, USA

The β-amyloid (Aβ) peptides associated with Alzheimer’s disease are generated by cleavage of the transmembrane C-terminal domain (C99) of the amyloid precursor protein by the enzyme {gamma}-secretase. Barrett et al. used nuclear magnetic resonance (NMR) and electron paramagnetic resonance spectroscopy to show that C99 contains surface-associated N- and C-terminal helices and a flexibly curved transmembrane helix that is well suited to processive cleavage by {gamma}-secretase. Elevated cholesterol levels have been found to increase Aβ generation. NMR titration together with mutagenesis revealed a binding site for cholesterol within C99 that included a motif previously implicated in protein oligomerization.

P. J. Barrett, Y. Song, W. D. Van Horn, E. J. Hustedt, J. M. Schafer, A. Hadziselimovic, A. J. Beel, C. R. Sanders, The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol. Science 336, 1168–1171 (2012). [Abstract] [Full Text]

Citation: V. K. Vinson, Insights into Amyloidogenesis. Sci. Signal. 5, ec160 (2012).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882