Protein ID'd As Alzheimer's Pathway

Wednesday, September 6th 2000, 12:00 am
By: News On 6

A newly identified protein that may be essential to early development and maintenance of the brain and other cells may also contribute to Alzheimer's disease late in life.

"It's rather poetic, really _ what makes you in the first place, sort of does you in," said Peter St. George-Hyslop of the University of Toronto, who reported the finding in Thursday's issue of the journal Nature.

The protein, which St. George-Hyslop and fellow Canadian researchers named nicastrin, binds itself to another protein, called presenilin, which is suspected of triggering the formation of deadly plaques, or buildups, in brain cells, causing Alzheimer's.

Nicastrin may also play a role in early fetal development by helping to determine how cells specialize into many forms, such as muscle, skin and brain cells.

Proteins typically have very specific functions, such as proteins that act as enzymes or hormones. Many simply cut or assemble other proteins into larger structures, and nicastrin may play that role with presenilin, researchers say.

"It is tragic indeed that this process might contribute to Alzheimer's disease in our old age," said Dale Schenk of Elan Pharmaceuticals in San Francisco.

In an accompanying commentary on the Canadian research, Schenk said the study could help lead to a new drug to slow or halt the progression of Alzheimer's.

The DNA in every living cell is coded to create amino acids that are linked together in chains called proteins. The more complex the protein, generally the larger the chain is.

St. George-Hyslop and his group purified the presenilin protein and found two types of other proteins that bound themselves to presenilin and made it larger. One of the two smaller types of proteins was already known, but the second had not previously been identified.

It was named nicastrin for the Italian village of Nicastro, where a pioneering study on Alzheimer's was done in the 1960s with an extended family suffering from the disease.

After identifying nicastrin, St. George-Hyslop and his team altered the genes of fruit flies, worms and mice to control for the amount of nicastrin produced.

They found they could either decrease or increase the main ingredient of Alzheimer's plaque by altering nicastrin levels.

But they also found nicastrin plays a fundamental role in natural protein synthesis early in life.

"This is part of the molecular machinery that is important because it evolved over billions of years," St. George-Hyslop said. "But it's also involved in generation of the protein that causes Alzheimer's disease."