Prions: Molecular and Cellular Biology Book Reviews

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Review by
Steve Dealler. The Pathology Laboratory, Burnley General Hospital, Burnley, BB10 2PQ. U.K.

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This book is absolutely the number one when it comes to having a good source of data on the molecular biology of prion disease. Each of the chapters, running from PrP structure to genetically modified mice contains the latest information in the subject that would be of value. Each of the authors is one of the top in the field and there is little missing from it. One of the worst articles is about the treatment perspectives by the Italian group and this includes almost solely their own work on iododoxorubicin. To some degree this is true about many of the authors, who have stuck to their own research paths rather than taking this opportunity to do a review. The book is a must for researchers and I have been waiting for it for some time.

Review by
CAB International

January 1999

The eleven chapters of this book cover structure and function of the prion proteins; pathology and treatment of prion diseases; the use of genetically modified mice in prion research; human prion diseases; bovine spongiform encephalopathy and new variant Creutzfeldt-Jacob disease, and the potential existence of yeast prions. Fifty two authors contributed to the book. There is an index.

Review by
David C. Bolton. Dept of Molecular Biology, NYS Institute for Basic Research, Staten Island, NY 10314-6399, USA.

Trends in Microbiology 7: 220. May 1999

My first introduction to prions (then called 'slow viruses' or 'transmissible spongiform encephalopathy agents') came in 1980, as I prepared to take a postdoctoral fellowship with Stanley Prusiner. The story, as much as was known, was as fascinating then as it is today. Prions are as sinister and insidious as any villain contrived in Hollywood, and the diseases they cause are tragic for the affected individuals and their families. Prior to 1985, prions and prion diseases were the obscure domain of a handful of laboratories in different parts of the world. The animal diseases were generally regarded as economically insignificant, and the human diseases, though fatal, were rare curiosities. However, the political perception (if not the scientific understanding) of prion diseases was rapidly transformed by the outbreak of bovine spongiform encephalopathy (BSE or mad cow disease) in the UK in 1985. The eventual enormity of the BSE epidemic and the fear that contaminated beef could transmit this fatal neurodegenerative disease of cattle to humans captured the attention of public health officials, scientists and politicians around the globe.

The 1980s also witnessed the beginning of the molecular era of prion research and the resurrection of the 'protein only' theory of prion structure and replication. In a fortunate chronological juxtaposition, advances in the characterization of scrapie prions provided many of the tools that would soon be needed to understand the BSE epidemic. Discovery of the prion protein (PrP) and its identification as both a component of the infectious prion and a product of a host gene helped explain many of the peculiar properties of prions. The 1997 Nobel Prize for Physiology and Medicine was awarded to Professor Prusiner in recognition of the pioneering work on prion purification and characterization that was carried out in his laboratory.

Prions: Molecular and Cellular Biology provides an interesting cross section of current research on prions and prion diseases. As the title implies, the book focuses mainly on the molecular, cellular and genetic aspects of prion biology. Three of the 11 chapters focus on the structure, folding and mis-folding of the prion protein, while two chapters review work on the metabolism of normal and mutant PrPs in cell culture systems. The pathophysiological roles of PrP are discussed in chapters that review studies with transgenic mice, neuroectodermal tissue transplants and PrP peptides. Other chapters review the human genetic prion diseases and the relationship between BSE and the new variant of human Creutzfeldt-Jakob disease. The final chapter develops specific criteria for defining prions in yeast and fungal systems using the yeast prions [URE3] and [PSI] as examples. Using these criteria, the authors propose that the [Het-s] trait in the filamentous fungus Podospora anserina results from a new fungal prion protein.

Although I found the book worthwhile, its quality is variable. The chapters on prion protein structure (Glockshuber et al.), cell biology (Harris), transgenic mice (Weissmann et al.), neuroectodermal transplants (Aguzzi et al.) and human genetic prion diseases (Young et al.) met or exceeded my expectations in terms of breadth of scope, clarity, insightful interpretation and thoroughness of the citations. However, other chapters fell short in one area or another and some were multiply deficient.

As is often the case, the book follows the format of a collection of individual papers rather than a unified work. Readers just concentrating on selected chapters will find this advantageous, but those who read the entire book might prefer a better integration of the subject matter between chapters. For example, inclusion of an introductory chapter would have eased readers unfamiliar with the field into the subject while obviating the need to repeat some of the background material at the beginning of each chapter.

The overall presentation of the book is satisfactory but not outstanding, and the quality of the figures varies. For example, the type in the body of the text is not always clear, and missing portions of letters were surprisingly frequent. This, together with the small font size, made reading some of the figure legends tiresome. Although these factors do not diminish the content of the book, they do detract from the reader's enjoyment. Prions: Molecular and Cellular Biology is not likely to become a classic, but it is worthwhile reading for active prion researchers or molecular and cell biologists who have more than a passing interest in this subject.

Review by
Yury O. Chernoff. School of Biology, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA

Trends in Genetics 15: 336. August 1999

It might have seemed to the general public in the early 1900s that the mission of physics was essentially complete. Just a few 'black spots' remained to be cleared up, such as the unexplained discrete nature of atomic spectra or the indeterminate phenomenon of radiation, for a coherent picture of the Universe to finally emerge so that physical science would be transformed into a technology dealing with predictable applications.

Of course, the deep thinkers thought otherwise. A century later, we now know that they were right and the 'public' was wrong. The 'black spots' produced concepts and applications that changed not only the face of physics but also our daily lives and the history of humankind in the 20th century. Furthermore, with all due respect to the achievements of physicists, the picture of the Universe remains as cloudy as ever.

The prion phenomenon represents a 'black spot' on the body of modern biology, and it might have a similar impact. The recent epidemic of 'mad cow disease' in the UK and the possibility of the transmission of this incurable and fatal disease to humans have heightened awareness of the medical aspect of this problem. However, prions are able to do even more harm. They challenge the central dogma of molecular genetics, which states that only nucleic acids can transmit genetic information. In the case of prion diseases, no nucleic-acid-containing agent that could be responsible for infection (such as bacteria or virus) has so far been identified. One of the models suggests that the wrongly shaped protein (prion protein) serves as the infectious agent itself because of its ability to convert normal protein into the wrong shape. The 1997 Nobel Prize in Medicine awarded to S. Prusiner, one of the pioneers of prion research, underlines the importance of this emerging field.

This new book, edited by the famous prion researcher David A. Harris, serves as a very interesting and detailed introduction to molecular and cellular aspects of prion biology, from structural studies of the prion protein to mechanisms of pathogenesis and the prospects of potential treatments for prion diseases. In vitro cell and animal experimental models of prion conversion and propagation are considered. Human prion diseases and epidemiological aspects of the transmission of 'mad cow disease' to humans are discussed. The book has an impressive line-up of contributing authors including such leaders in the prion field as A. Aguzzi, B. Caughey, B. Chesebro, D. Dormont, P. Gambetti, B. Ghetti, R. Glockshuber, C. Weissmann, R. Wickner and others. It should certainly be useful for the wide audience of biologists and physicians who are interested in gaining first-hand exposure to the field.

One minor criticism is that the book focuses almost exclusively on one example of a prion, the mammalian PrP. Recent evidence, as Wickner was the first to point out (1), suggests that there is a wider distribution of the prion phenomenon in nature. This gap is filled in part by the chapter written by Masison and colleagues, which summarizes information on yeast and fungal prions. However, further comparisons with other potentially related experimental models would certainly be useful. Cortical inheritance in ciliates is one example of a protein- based hereditary system that exhibits remarkable similarities to prions (2, 3). The cytoskeletal structures, in general, possess a clear potential for the 'template- like' assembly that could serve as a molecular basis for transmission of structural (as opposed to sequential) information in cell generations. Exploration of such possibilities would be especially useful in the light of recent models suggesting that prion transmission occurs via the process of nucleated polymerization, which possesses remarkable similarities to the assembly of the cytoskeletal structures (4). On the other hand, aggregation-related disorders such as Alzheimer's disease exhibit many similarities to prion diseases and could also be discussed in such a context. This would place the material in a wider evolutionary and medical perspective, and emphasize the potential role of information proteins in heredity and pathogenesis. However, this does not diminish the importance of this book, which reviews one of the most exciting areas of modern biology.

References
1. Wickner R.B. (1994) Science 264: 566-569.
2. Beisson, J. and Sonneborn, T.M. (1965) Proc. Natl Acad. Sd. U.S.A. 53: 275-282.
3. Hyver, C. and LeGuyader, H. (1995) C. R. Acad. Sci. 318: 375-380.
4. Lansbury, P.T. and Caughey, B. (1995) Curr. Biol. 2: 1-5

Review by
Jim Hope. Institute for Animal Health, Compton, UK

Microbiology Today 26: 145. August 1999

David Harris has drawn together a cosmopolitan band of experts to cover a broad area of work on prion diseases and succeeded in producing a monograph which is both readable and erudite. This book is a must for those of us working in the field or for harassed tertiary-grade teachers looking for a primer to prepare a set of up-to-date lectures on prions. I read it cover-to-cover in a weekend and it will remain a well-thumbed text in our lab for several years to come; the quality of the writing and its scientific accuracy probably justifies the price. I've one minor, xenophobic quibble - no Brits! However, the demands of the BSE Inquiry rather than editorial oversight may have prevented British researchers from adding their inside knowledge of BSE and vCJD to this text and these hot topics are dealt with authoritatively by D. Dormont. All the other authors have reviewed their own contribution to the field and so, apart from a necessarily repetitive introduction in each chapter, their personal enthusiasm, perspective and feel for the subject are powerfully communicated. The chapters on the 3D-structure of PrP and yeast prions were especially good.