Two European groups have proposed
strategies for treating Alzheimer's disease that are focused on hitting
intermediate protein fragments and enzymatic steps in the pathway that produces
A team at Institut National de la Santé et de la Recherche Médicale and the University of Nice Sophia Antipolis thinks the goal should be reducing levels of C99,
a protein fragment that is a precursor of b-amyloid. A team at Catholic University Leuven expects that hitting a newly identified cofactor of g-secretase
can yield the same effect as eliminating C99 and b-amyloid while
potentially acting more selectively on the b-amyloid pathway than g-secretase
Previous work by other researchers showed
that C99 overexpression was highly toxic to cultured neurons, suggesting the
APP cleavage intermediate could contribute to AD pathology independently of Ab.4
The big question is whether C99 plays a
role in human disease, but answering this is technically challenging.
Meanwhile, De Strooper's team is
identifying proteins that interact with g-secretase and could
be targeted with safer compounds than the failed broad-spectrum inhibitors.
Osherovich, L. SciBX 5(47); doi:10.1038/scibx.2012.1225 Published online
Dec. 6, 2012
1. Lauritzen, I. et al.
J. Neurosci.; published online Nov. 14, 2012; doi:10.1523/JNEUROSCI.2775-12.2012
Contact: Frédéric Checler, University of Nice Sophia Antipolis,
Sophia-Antipolis, France e-mail: firstname.lastname@example.org
2. Thathiah, A. et al.
Nat. Med.; published online Dec. 2, 2012; doi:10.1038/nm.3023 Contact:
Bart De Strooper, Catholic University Leuven, Leuven, Belgium e-mail: email@example.com
Contact: Amantha Thathiah, same affiliation as above e-mail: firstname.lastname@example.org
3. Citron, M. Nat. Rev.
Drug Discov. 9, 387-398 (2010)
4. Jin, L.-W. et al. J.
Mol. Neurosci. 19, 57-61 (2002)
5. Osherovich, L. BioCentury
19(44), A8; Oct. 24, 2011
6. Thathiah, A. et al.
Science 323, 946-951 (2009)
AND INSTITUTIONS MENTIONED
Bristol-Myers Squibb Co. (NYSE:BMY), New York, N.Y.
Catholic University Leuven, Leuven, Belgium
Elan Corp. plc (NYSE:ELN), Dublin, Ireland
Eli Lilly and Co. (NYSE:LLY), Indianapolis, Ind.
Galapagos N.V. (Euronext:GLPG; Pink:GLPYY), Mechelen, Belgium
Institut National de la Santé et de la Recherche Médicale, Sophia-Antipolis, France
Johnson & Johnson (NYSE:JNJ), New Brunswick, N.J.
Perelman School of Medicine at the University of
Pfizer Inc. (NYSE:PFE), New York, N.Y.
University of Nice Sophia Antipolis, Sophia-Antipolis, France