Abstract
Strange as it may sound nowadays, people of Middle Ages hardly recognized cancer as a major problem. This is not because cancer did not exist. Rather, it is because the average person had a much higher chance of dying for a different reason, such as plague or smallpox epidemics that could wipe out entire countries in a matter of months. Microbial infections are still a problem, but certainly the dangers they cause are not as grave as they were several centuries ago.
Strange as it may sound nowadays, people in the Middle Ages hardly recognized cancer as a major problem. This was not because cancer did not exist. Rather, it was because the average person had a much higher chance of dying from a different reason such as plague or smallpox epidemics that could wipe out large populations in a matter of months. Microbial infections are still a problem, but certainly the dangers they cause are not as grave as they were several centuries ago.
It is primarily due to successes in the biomedical disciplines in their fight against microbial infections that cancer and heart disorders now outrank microbial infections as one of the major problems troubling modern societies. Cancer and heart disorders are now under attack, and the power of modern biology is being mobilized to decipher their mechanisms and to produce cures. If the biomedical research enterprise fulfills this task as successfully as the previous ones, what is our next major enemy going to be? About half of the individuals who reach the age of 85 develop Alzheimer's disease. This disorder, which leads to extensive neurodegeneration and makes patients' lives miserable, is fatal and incurable. The same is more or less true for other protein assembly disorders of a similar nature. These diseases cause significant problems today. But if we want to live longer, we must face them as our major obstacle in the near future.
Some protein assembly disorders generate protein aggregates that grow as molecular “tumors” no longer controlled by the cellular defense systems. Moreover, some of those “tumors” acquire the ability to spread to other cells or organisms, thus becoming infectious agents composed of proteins. Such agents are harder to deal with than microbial infections; because they are not “alive” in the common meaning of this word, they cannot be killed. This year marks the 10th anniversary since the Nobel Prize was awarded to Stanley Prusiner who promoted what initially looked like a heretical idea of a protein (called a prion) being capable of transmitting infection. Prion diseases, such as “mad cow disease” which is transmissible to humans, represent a threat serious enough to cause concern on their own. However, the biological significance of the prion phenomena goes far beyond specific medical concerns. The prion concept implicates proteins as information carriers, therefore challenging—or, more accurately, amending—the central dogma of molecular biology.
Indeed, prions have been found in yeast and fungi where they manifest themselves as infectious factors transmitted via cytoplasm, or in other words, as non-Mendelian heritable elements. Moreover, it appears that a wide variety of proteins can form ordered aggregates (amyloids) in specific conditions and/or when their folding is impaired. These and other data indicate that the amyloid fold, which is a major characteristic of the majority of known prions, may represent a very ancient protein fold, potentially playing a role not only in pathology but also in the biologically adaptive processes. To complicate matters even further, yeast and fungal prion phenomena are not restricted to protein aggregation; there have also been examples of self-perpetuating covalent protein modifications. It has been known for years that in some Protozoa entire multicomponent structures can be inherited in a “prion-like” fashion so that a pre-existing complex serves as a “template” for the assembly of a newly generated complex.
After publishing one of my papers dealing with yeast prions, I received a letter from a biologist working in a different field who angrily dismissed prions as pseudoscience on the grounds that such a concept contradicted, in his understanding, the basic laws of biology. This letter pointed my attention to the fact that even the biological community as a whole has difficulties placing the prion phenomena into a general picture of molecular processes occurring in biological systems. It certainly does not help that the evidence for prions, other protein assembly disorders, and structural inheritance phenomena has been accumulated in different experimental models and by using very diverse techniques. As a result, even researchers studying these processes frequently speak different scientific languages, publish their papers in different journals and do not necessarily appreciate general implications that unify and integrate their approaches. This is why members of our Editorial Board and I responded enthusiastically to the proposal by our publisher, Ron Landes, to establish a new journal that would provide a home for publications covering various aspects of our newly emerging field.
With this in mind, I am happy to introduce the inaugural issue of Prion, a journal that intends to cover the entire area of protein assembly processes and structural inheritance with all their biological and clinical implications. To emphasize this broad focus and integrative approach from the very beginning, this first issue of Prion combines papers on mammalian and yeast prions with a set of minireviews written by the participants of the Jacques Monod Conference on Protein Misfolding and Aggregation in Ageing and Disease. We sincerely hope that both readers and new contributors take advantage of this new forum and that with their help Prion will take its rightful place on the road from Gene and Proteins to Cell, Development and Evolution.