Table Of ContentPRIONS
The New Biology
of Proteins
PRIONS
The New Biology
of Proteins
CLAUDIO SOTO
Boca Raton London New York
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Dedication
To Claudia, Andres, Kevin, Dylan, and my little girl to be.…
Preface
Transmissible spongiform encephalopathies (TSEs), also known as prion-
related diseases, are a group of infectious, fatal neurodegenerative disorders
for which there is no cure, treatment, or early diagnosis. TSEs are dramatic
diseases that rapidly, progressively, and inexorably destroy the cognitive,
motor, and sensorial skills that are the essence of human beings. At the
molecular level, the disease is likely caused by the misfolding of the prion
protein, which accumulates in the brain and produces neurodegeneration.
Several unprecedented scientific findings, which have directly confronted
popular dogmas in biology, have put prion research in the spotlight. The
experimental evidence strongly supports an entirely novel disease mecha-
nism, involving disease transmission by replication of the misfolding of a
single protein in the absence of nucleic acids. The popularity of prion dis-
eases is also due to the panic produced by the recent appearance of a new
human disease (variant Creutzfeldt-Jakob disease) that is transmitted by
eating meat contaminated by bovine spongiform encephalopathy (BSE), bet-
ter known as mad cow disease. Because of insufficient information available
regarding the incubation time and the actual level of exposure to the con-
taminated material, it is impossible to make any well-founded prediction
about the future of this nascent epidemic.
This book attempts to combine a detailed and up-to-date description of
the state of the knowledge in the field with an intriguing but tempered
speculation of the putative implications of the findings to our current under-
standing of biology. During the last few years we have begun to perceive
the broader implications of the heretically attractive prion concept of trans-
mission of biological information by propagation of alternative protein fold-
ing. I hope that this book can contribute to liberating the imagination of the
reader to see the new scientific world opened by prions, which impact
broader areas of biology, public health, and biotechnological strategies for
therapy and diagnosis.
Although I regretted it many times during the long process of preparing
this book, I decided to write it entirely myself in order to give continuity to
the text, maintain a homogenous style, and provide an appropriate connec-
tion between chapters. The decision was also guided by a desire to avoid
important gaps and repetitions, which are frequent in multiauthored books.
I could not have completed this book without the constant support of my
family, lab members, and close collaborators. To them I extend my sincere
gratitude for their patience, help, and illuminating discussions.
Author
Claudio Soto is currently the Charlotte-Warmoth professor of neurology,
human biological chemistry and genetics, and neuroscience and cell biology,
and director of the Protein Misfolding Disorders Research Unit at the Uni-
versity of Texas Medical Branch in Galveston. Dr. Soto was recently awarded
the Green Distinguished University Chair in Neurosciences and was
appointed Director of the new George and Cynthia Mitchell Center for
Alzheimer’s Disease Research. He received his Ph.D. in biochemistry and
molecular biology from the University of Chile in 1992 and was a postdoc-
toral fellow at the Catholic University of Chile and at the New York Univer-
sity School of Medicine, where he became an assistant professor of research
in 1995. Between 1999 and 2003, Dr. Soto was senior scientist, head of the
Department of Molecular Neuropathology, and scientific advisor for neuro-
biology at Serono International in Switzerland. For the past 12 years, he and
his colleagues have engaged in research into the molecular basis of neuro-
degenerative diseases associated with the misfolding of proteins and their
accumulation in the brain, focusing particularly on Alzheimer’s and prion-
related disorders. His work has led to the development of novel strategies
for treatment and diagnosis of neurodegenerative diseases.
Dr. Soto has published more than 80 scientific articles in some of the
most prestigious peer-reviewed journals. He has received numerous awards
and has been invited to give presentations at more than 50 international
meetings worldwide. Dr. Soto is a member of the editorial board of several
scientific journals and has acted as adviser and reviewer for many institu-
tions, including the World Health Organization, the U.S. National Institutes
of Health, and the European Commission, among others.
