How To Reach C&ENACS Membership Number


 

March 22, 2004
Volume 82, Number 12
CENEAR 82 12 p. 8
ISSN 0009-2347


NEUROCHEMISTRY

INFLAMMATION VERSUS THE BRAIN
Evidence mounts that inflammation is involved in neurodegenerative disease

SOPHIE ROVNER

Chronic inflammation is getting a bad name for its presumed role in several diseases—and new research shows that its notoriety may be well deserved.

A team led by Jeffery W. Kelly, a chemistry professor at Scripps Research Institute, suggests that abnormal cholesterol and lipid metabolites produced as a result of inflammation bond with normal amyloid peptides in the brain. These reactions increase the peptides’ hydrophobicity, predisposing them to misfold. The misfolded peptides then aggregate into the neurotoxic fibrils characteristic of Alzheimer’s disease [Proc. Natl. Acad. Sci. USA, published online March 15, http://www.pnas.org/cgi/doi/10.1073/pnas.0400924101].

GOOD AND BAD Nicotine [below, right) dampens brain inflammation, but cholesterol metabolites such as the one shown (below, left) promote it.

The inflammatory process involves several types of cells and signaling compounds in a complicated cascade. In the peripheral nervous system, one control point for the cascade centers on the binding of acetylcholine to macrophages, which curtails the cells’ inflammatory response. Last year, Kevin J. Tracey and colleagues at the North Shore Long Island Jewish Research Institute in Manhasset, N.Y., identified the binding site on the blood-borne macrophages as an 7 nicotinic acetylcholine receptor [Nature, 421, 384 (2003)].

New results from the University of South Florida (USF), Tampa, suggest that a similar control mechanism might exist in the brain. USF neuroscientists Jun Tan and R. Douglas Shytle and their colleagues show that the 7 receptor can be found on the brain’s microglial cells, which mediate immune response in the central nervous system [J. Neurochem., published online March 8, http://www.blackwell-synergy.com/links/doi/10.1046/j.1471-4159.2004.02347.x].

ANTI-INFLAMMATORIES Tan and Shytle suss out nicotine’s benefits.
ERIC YOUNGHANS/UNIVERSITY OF SOUTH
Microglia in patients with diseases such as Alzheimer’s and Parkinson’s become excessively active, which “gives rise to persistent inflammation, resulting in exacerbation of neurodegeneration,” the USF team hypothesizes.

Smoking appears to provide some protection against such diseases. The researchers believe binding of nicotine to the glial cells’ 7 receptors suppresses their inflammatory activity. Thus, mimics of nicotine that avoid its side effects could potentially be used as preventatives for neurodegenerative diseases.

The work, which the authors concede is preliminary, “is very interesting and intriguing and should be followed up,” says Jerrel L. Yakel, who studies acetylcholine receptors at the National Institute of Environmental Health Sciences.



Top


Chemical & Engineering News
Copyright © 2004 American Chemical Society



 
Related Stories
DEPRESSION
[C&EN, Feb. 9, 2004]

What's Behind Amyloid Diseases
[C&EN, Aug. 12, 2002]

Combating Alzheimer's
[C&EN, Mar. 11, 2002]

Related Sites
Jeffery W. Kelly

Jun Tan

E-mail this article to a friend
Print this article
E-mail the editor
   

Home | Table of Contents | Today's Headlines | Business | Government & Policy | Science & Technology | C&EN Classifieds
About C&EN | How To Reach Us | How to Advertise | Editorial Calendar | Email Webmaster

Chemical & Engineering News
Copyright © 2004 American Chemical Society. All rights reserved.
• (202) 872-4600 • (800) 227-5558

CASChemPortChemCenterPubs Page