Nobel To Prion Professor
By Sean Henahan, Access Excellence
 San
Francisco, CA (10/6/97)- Stanley Prusiner (pictured), whose suggestion
of a new infectious particle called the prion was originally greeted with
skepticism has received the ultimate vindication, the Nobel Prize for Medicine
and Physiology.
The Nobel Committee cites Prusiner " for his pioneering discovery of
an entirely new genre of disease-causing agents and the elucidation of
the underlying principles of their mode of action." Prusiner, a professor
of biochemistry at the University of California, San Francisco, was the
first to suggest the existence of prions and to suggest that they were
the causative agents of the spongiform encephalopathies- among them kuru
and bovine spongiform encephalopathy ("mad cow disease".)
Prions are rogue proteins that wreak havoc in the brains of infected
animals and people. They contain no nucleic acid (DNA or RNA). These hard
to classify biological objects consist of a single molecule containing
about 250 amino acids, termed the PrP protein. They are abnormal variant
of proteins that occur normally in cells, such as human brain cells. The
abnormal PrP proteins, when they enter the body, are able to convert their
normal counterparts into more of the abnormal forms.
Prusiner's research showed that the difference between the normal and
abnormal proteins did not lie in their primary structure (the sequence
of their amino acids), but rather in their folding -the abnormal PrP proteins
are folded in a way that allows them to resist normal protease degradation
so that over time this leads to the build up of aggregates of PrP, especially
in neurons in the brain. These aggregates resemble the tangles of abnormal
protein found in neurons in Alzheimer s disease patients.
"Prions are the only "life forms" that break the great "central dogma"
of biology. That is, we have come to expect that all life forms from viruses
to bacteria to plants to humans to hand down the blueprints for all their
progeny via their DNA (except for some viruses which carry their blueprints
as an RNA genome), and we expect that the process for converting the blueprints
into building blocks must involve replication of DNA, transcription of
the message into RNA, and translation of the RNA s message to form proteins,
the building blocks of cells, tissues, organs and whole organisms. Here
we have life forms where abnormal proteins, the PrP proteins, direct the
refolding of normal proteins just by direct contact," explained Dr. Frederick
A. Murphy, former Dean of the School of Veterinary Medicine, University
of California, Davis, in an interview
with AE.
Prions have been implicated in a number of spongiform encephalopathies,
including: scrapie, a disease of sheep; bovine spongiform encephalopathy
(BSE), a disease of cattle; and Creutzfeldt-Jakob disease (CJD), a disease
of humans. Prions jumped to the front pages when epidemiological and post-mortem
pathology studies confirmed an apparent link between BSE (mad cow disease)
and the human disorder CJD.
"Stanley Prusiner's discovery provides important insights that may furnish
the basis to understand the biological mechanisms underlying other types
of demential-related disease, for example Alzheimer's disease, and establishes
a foundation for drug development and new types of medical treatment strategies,"
the Nobel Committee notes.
Dr. Prusiner provides an update on prion science in the October
10, 1997 issue of Science
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