ERROR 1
ERROR 1
ERROR 2
ERROR 2
ERROR 2
ERROR 2
ERROR 2
Password and Confirm password must match.
If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)
ERROR 2
ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.
Cell-membrane-spanning protease enzymes called β-secretases play a critical role in β-amyloid peptide formation, a key step in the progression of Alzheimer's disease. Although several small-molecule inhibitors are capable of shutting down β-secretase's activity, many of them are inactive on intact cells, limiting their potential as Alzheimer's therapies. A multi-institution team led by Kai Simons of the Max Planck Institute of Molecular Cell Biology & Genetics in Dresden, Germany, has now shown that affixing such an inhibitor to the plasma membrane makes it more effective at stopping β-secretase (Science 2008, 320, 520). The researchers linked a peptide that inhibits β-secretase to a sterol, which targets the inhibitor to cholesterol-rich "lipid raft" sections of the membrane. In cell cultures, the new inhibitor effectively reached endosomes, the membrane-bound compartments inside cells where most β-secretase activity takes place. The inhibitor also reduced β-amyloid production in a mouse model of Alzheimer's. The anchoring approach may prove useful for targeting other disease-causing membrane proteins as well, the authors write. Simons is a founder of Jado Technologies, a Dresden-based company that is focusing on cell-membrane chemistry involving lipid rafts to address Alzheimer's and other diseases.
Join the conversation
Contact the reporter
Submit a Letter to the Editor for publication
Engage with us on X