Prion-related diseases, known as transmissible spongiform encephalopathies (TSEs), are infectious, fatal neurodegenerative disorders for which there is no cure, treatment, nor even a means for early diagnosis. The horrific advent of Mad Cow Disease -- transmitted to humans through eating meat from steers sickened by bovine spongiform encephalopathy --brought prion-related diseases international attention. Exceptionally dramatic, these diseases progressively and inexorably destroy the cognitive, motor, and sensorial skills that are the essence of human beings.
Prions: The New Biology of Proteins provides a well-organized overview of what is known about prion-related diseases. This comprehensive work reviews the symptoms, epidemiology, and neuropathology of the disease. It focuses on evidence supporting the idea that TSEs result from a novel disease mechanism: transmission by replication of the misfolding of a single protein in the absence of nucleic acids. Following this hypothesis, the book examines the structure, conversion, and mechanism of prion propagation and details its cellular biology. It explores the transmission, discusses the challenges involved with diagnosis, and considers various therapeutic avenues that are presently being explored.
A cohesive volume that integrates the pioneering work of many researchers, this book is authored by Claudio Soto, an internationally renowned researcher whose innovative work has led to an increased understanding of the heretical biology of prions and the development of novel strategies for treating and diagnosing neurodegenerative diseases.
As protein misfolding diseases are his specialty, Soto also looks at the phenomenon from a wider perspective. He examines other diseases that display folding aberrations, considers how commonly such aberrations occur in nature, and asks readers to open their minds to consider the impact of prions on broader areas of biology, public health, and biotechnological strategies.
Table of Contents
Each chapter ends with a concluding summation and references
Human and animal diseases: clinical symptoms, epidemiology, and neuropathology
The infectious agent and the prion hypothesis
Hypothesis for the infectious agent
Evidence supporting the prion hypothesis
Criticisms of the prion hypothesis
In vitro generation of prions
The prion protein: structure, conversion, and
mechanism of propagation
Structural features of the cellular and scrapie prion protein isoforms
Molecular mechanism of PrPC to PrPSc conversion
Other factors involved in PrP conversion
Peptide models used to understand PrP structure and conversion
Cell biology, genetic and putative function of the normal prion protein
Cellular biology of the normal prion protein
A signaling role for the prion protein?
PrP ligands indicate a potential role in apoptosis
A putative role of PrP in copper metabolism
PrP knockout animals and doppel
Prion strains, species barriers, and multiple
conformations of the prion protein
Multiple conformations of PrP
From the mouth to the brain
Prions in the gastrointestinal tract
The immune-system connection
From the lymphoid organs to the brain: peripheral nerves or blood–brain barrier?
Neurodegeneration in prion diseases
Characteristics of brain degeneration
Is PrP the cause of TSE neurodegeneration?
Mechanism of neuronal apoptosis
Neuronal apoptosis in TSEs involves the ER-stress pathway
A role for the proteasome in TSE pathogenesis?
The diagnosis problem and current tests
Importance of early diagnosis
Difficulties of diagnosis
Current status of TSE diagnosis in humans
Postmortem detection of BSE in cattle
The need for detection of PrP in blood
Novel approaches under development for premortem early diagnosis
PrP concentration by binding to specific ligands
Targets for TSE therapy
Compounds under development for TSE treatment
Cyclic amplification of prion protein misfolding: rationale, applications, and perspectives
The rationale behind PMCA
Applications of PMCA in prion diagnosis
In vitro generation of infectious prions by PMCA
Application of PMCA to understand the prion replication process
Other diseases of protein misfolding
Protein misfolding and disease
Structural determinants of misfolding and aggregation
Mechanism and driving forces in protein misfolding and aggregation
Kinetics and intermediates of misfolding and aggregation
Interactions between misfolded proteins
Prions: a common phenomenon in biology?
The yeast prions
The inherent infectious nature of misfolded aggregates
Why are protein misfolding disorders other than TSE not infectious?
How common is the prion phenomenon in nature?
“This volume provides a well-organized overview of that is presently known about prion-related diseases. This comprehensive work reviews the clinical symptoms, epidemiology and neuropathology of the diseases. It focuses on evidence supporting the idea that TSEs result from an entirely novel disease mechanism, involving transmissions by replication of the misfolding of a single protein in the absence of nucleic acids. … the book examines the structure, conversion, and mechanism of prion propagation and details its cellular biology. It explores the transmission of these diseases, discusses the challenges involved with diagnosis, and considers the various therapeutic avenues that are currently being explored. ”
— In Anticancer Research, Vol. 26, 2006
“… describes the current state of knowledge about the enigmatic world of prion diseases. The book is organized into 12 mostly brief chapters, which nicely summarize the various types of prion diseases and the challenges associated with their diagnosis and treatment. These sections review the biology of prions, the underlying hypotheses for prion replication, and the biochemical basis for strain diversity. … the book can be a valuable resource for scientists beginning to understand the world of prion diseases, the underlying biochemical mechanism of disease occurrence, and the challenges associated with the diagnosis and treatment of prion diseases.”
— Ermias D. Bealy, Centers for Disease Control and Prevention, Atlanta, Georgia, in EID – Emerging Infectious Disease, Vol. 13, No. 6, June 2007