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basis of new treatments for the memory-stealing disorder.

In 1995, Kun Ping Lu of Beth IsraelDeaconess Medical Center in Boston andTony Hunter of the Salk Institute for Bio-logical Studies in La Jolla, Calif., discov-ered Pin1. They subsequently showed thatit interacts with a protein called tau, animportant component of one of the twobrain lesions seen in Alzheimer’s disease.Known as tangles, these snarls of tau fil-aments turn up inside nerve cells. In con-trast, the other lesion consists of an abnor-mal buildup outside nerve cells of a proteinfragment known as beta-amyloid.

Most neuroscientists favor the hypothe-sis that beta-amyloid triggers the brain-cellloss in Alzheimer’s disease, but some arguethat tau is equally, if not more, important.Tau protein normally shapes a cell’s inte-rior skeleton, but in Alzheimer’s disease,molecular tags called phosphates get addedto tau. This embellishment seems to pro-mote tangle formation.

Lu, Hunter, and their colleagues hadshown that Pin1 binds to tau overloadedwith phosphates. This alters the protein’sshape in such a way that those tags get shed.“It’s important for restoring the function oftau,” says Lu.

This finding and others persuaded Luthat Pin1 can protect brain cells from theravages of tangles. Some investigators, how-ever, interpreted the data differently, argu-ing that the enzyme actually contributes totangle formation.

In the July 31 Nature, Lu, Hunter, andtheir colleagues report that micewith an inactive Pin1 gene suf-fer nerve cell loss in thespinal cord and brainas the animals age. Themice show decreasingmobility and generalloss of muscle coordina-tion.

A close examination ofthe brains of the micerevealed that select regionsexhibited nerve cell degener-ation. In those areas, tau pro-teins were studded withphosphates and were tan-gled. Other researchers haveinduced tangle formation inmice by giving the rodentsextra copies of the human taugene but not by inactivatinga gene, says Lu.

“This is the first demonstration thatmouse tau can form structures similar towhat we see in human brain,” adds MarkSmith of Case Western Reserve Universityin Cleveland. “It will be a useful model toclarify the connection between tau and neu-rodegeneration.”

While studying preserved brain tissuefrom people who had Alzheimer’s disease,

Lu and his colleagues also found thatregions with the highest concentrations ofPin1 had the lowest percentages of nervecells with tangles. Moreover, in healthybrains, the highest concentrations of theenzyme appear in areas that Alzheimer’sdisease doesn’t normally destroy, the sci-entists report.

The animal and human data togethercreate a “strong case” that Pin1 protectsagainst Alzheimer’s disease, says D. StephenSnyder of the National Institute on Agingin Bethesda, Md.

Smith isn’t quite as convinced, noting thatthe mutant mice experience nerve cell loss inbrain regions different from those afflicted byAlzheimer’s disease. “I’m not sure this [newstudy] shows the role of Pin1 in Alzheimer’sdisease as much as it shows a role in neu-rodegeneration,” he says. —J. TRAVIS

Worm’s JawsShow MettleZinc links may inspirenew materials

Since biology excels at making strong andhard substances, such as bone, teeth, andseashells, scientists who design new mate-rials often try to emulate nature’s inven-tions. For Galen D. Stucky of the Universityof California, Santa Barbara and his col-leagues, the microstructures of marine

worms’ jaws harbor cluesfor making synthetic

materials. Unlike thebony jaws of mam-mals, these worms’

chops are made pri-marily of protein.

Stucky and hiscoworkers recently

reported that thetiny jaws of thebloodworm, Glyc-era dibranchiata,

contain the copperchloride mineral called

atacamite, which makes thestructures particularlystrong (SN: 11/9/02, p. 302).In an upcoming issue of theProceedings of the NationalAcademy of Sciences, theresearchers compare the

bloodworm’s jaws to those of the clamworm, Nereis limbata, a sand- and mud-dwelling scavenger. Although the proteincompositions of the two worms’ jaws aresimilar, the jaws of Nereis contain zincinstead of copper.

Using a variety of tests, Stucky and hiscoworkers found that the properties of theclam worm’s jaw vary with its zinc content.

As the concentration of zinc increases, so dothe jaw’s hardness and stiffness. The clam-worm jaws are especially hard near the tips,says Stucky, but even there, they’re stillsofter than bloodworm jaws.

The researchers also found that the zinc inclam-worm jaws isn’t in a mineralized form,as is the case for much of the copper in thetip of the bloodworm jaws. Instead, the teamdetermined that clam-worm jaws are hardwherever zinc cross-links protein networks.

Stucky and his coworkers suggest thateach animal’s jaw composition suits themechanical demands of its eating habits.The clam worm, which scavenges food, maynot require jaws as hard as those of thebloodworm, which thrusts its jaws into preyto inject venom.

In the future, notes materials researcherMehmet Sarikaya of the University ofWashington in Seattle, investigators mightdiscover more specifically how the zinc-based cross-linking occurs in clam wormsand why the animals rely on zinc ratherthan on another metal. Within such knowl-edge, Sarikaya says, scientists might findclues for designing their own hardy com-posites of proteins and metals.

Stucky says his group is already takingsteps toward creating flexible and light-weight materials inspired by the worm. Theresearchers are also examining the hardbeaks of octopuses and squid, which areprotein based like the worms’ jaws yet con-tain little or no metal.

Materials scientists can learn a lot fromanimals, says Arthur Heuer of Case West-ern Reserve University in Cleveland, wherehe has studied the conch shell for clues tomaterials design. Says Heuer: “Nature hashad hundreds of millions of years to exper-iment.” —J. GORMAN

TransplantHopeNew thymus tissue jump-starts immunesystem in babies

Babies born without a thymus gland—andtherefore bereft of a functioning immunesystem—are easy prey for disease-causinginvaders. If untreated, this deficiency, calledsevere DiGeorge syndrome, is invariablyfatal before a child’s third birthday.

For babies with the syndrome, also calledDiGeorge anomaly, a thymus transplantmay present a life-changing option. But sci-entific information on such transplants hasbeen limited to the results of sporadic casestudies because the disease is rare, affect-ing only a handful of newborns each yearin the United States. Researchers at DukeUniversity Medical Center in Durham, N.C.,

JAW INNARDS X-rayabsorption (top) showsthe highestconcentration of zinc(dark area) near the tip ofa clam-worm jaw. A light-microscope image of thejaw, about 3 millimeterslong, appears at bottom.

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