Alzheimer's Disease

IISc alumnus study links moss protein to Alzheimers Disease

An Indian Institute of Science, Bangalore alumnus has shown that the moss plant Physcomitrella patens has a surprising link with an amyloid plaque found in brains having Alzheimers disease.

Washington, February 9 : An Indian Institute of Science, Bangalore alumnus has shown that the moss plant Physcomitrella patens has a surprising link with an amyloid plaque found in brains having Alzheimer's disease.

Abha Khandelwal, a post-doctoral researcher at Washington University in St. Louis, says that she has discovered in the moss the presence of the gene presenilin (PS), which in mammals provides the catalytic activity for an enzyme called gamma secretase.

This enzyme cuts important proteins Notch, Erb4 and the amyloid precursor protein (APP), all key components of communication channels that cells use to arbitrate functions during development.

Notch is a part of a short-range mammalian communication channel, and for years it has been known to have a working relationship with PS. However, Notch is absent in plant cells.

With a view to understanding what PS was doing in moss, she collaborated with Raphael Kopan, a professor of molecular biology and pharmacology at the Washington University School of Medicine. The researchers removed PS from the plant for the purpose.

They found that moss lacking PS looked different, growing with straight, rigid filaments instead of curved and bent filaments like the parent moss with the PS gene intact.

"That showed the gene has an obvious function that clearly did not require Notch. We just don't know exactly what it is yet, but we have proposed a hypothesis to be tested," said Dr. Ralph S. Quatrano, in whose laboratory the experiment was conducted.

The researchers then took the phenotype, switched out a mammalian form of PS into it, and rescued it.

They revealed that inserting the moss gene in mammalian cells resulted in reversing some of the losses experienced by animal cells lacking PS function, testifying that the human and moss proteins had an evolutionary conserved function.

"In the moss, the proteins were very nearly interchangeable. This suggested that PS has a role outside the Notch pathway and may provide clues in mammalian systems as to its primary role, independent of its substrate in mammalian cells," Quatrano said.

Khandelwal added: "We were amazed to realize that genes from moss and humans were not only structurally conserved but also shared similar functions."

The researchers believe that the outstanding plant model may be used not only to understand some of the off-target affects during Alzheimer's Disease therapy, but also to unravel novel interactions and pathways in plants.

The study has been reported in the Proceedings of the National Academy of Science.

ANI