Web Date: May 21, 2008
Fellutamide B Taps Proteasome To Aid Neurons
The natural product fellutamide B aids brain cells by inhibiting the proteasome, the cell's garbage disposal for proteins, Yale researchers have found. The finding could aid the design of drugs that promote the well-being of neurons.
Craig M. Crews and coworkers show that fellutamide B, a small molecule isolated from a marine fungus, binds to caspase-, trypsin-, and chymotrypsin-like regions of the proteasome via a threonine residue. This binding inhibits enzyme-catalyzed protein hydrolysis in the proteasome, which, in turn, activates transcription of a polypeptide called nerve growth factor (NGF) (Chem. Biol., DOI: 10.1016/j.chembiol.2008.03.020).
NGF, which protects existing neurons and can repair those damaged by injury or disease, has shown potential for treatment of neuronal injuries such as stroke as well as Parkinson's and Alzheimer's diseases. However, when administered directly, NGF cannot cross the blood-brain barrier, greatly limiting its potential as a treatment for such diseases. Fellutamide B, in contrast, is small enough that it potentially could cross the blood-brain barrier and stimulate NGF synthesis within brain cells. The better understanding of fellutamide B afforded by this study may spur the development of other small-molecule therapies that protect and repair neurons.
- Chemical & Engineering News
- ISSN 0009-2347
- Copyright © American Chemical Society