Biomed Middle East

Beneficial Role of Prions in Brain Function

Prion infection cycle

A prion is an infectious agent, composed primarily of protein.  The word “prion” is taken from the longer term “proteinaceous infectious particle.”  Prions are hypothesized to infect and propogate by refolding abnormally into a structure which is able to convert nomal  molecules of the protein into the abnormally structured form.  All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets.  This altered structure is extremely stable and accumulates in infected tissue, causing tissue damage and cell death.  Prions differ from other pathogens such as viruses, bacteria, fungi and parasites in that they do not contain deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that affect both humans and animals.  Kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker disease are the prion diseases that cause illness in humans. All three diseases cause damage to the person’s brain and always lead to death.

Normal and abnormal prion condition

Accordingly, prions possess a hazardous status.  Regardless of this depressing nature, a recent research describes certain essential positive responsibilities of prions in brain function. A persistent problem in the study of memory is how molecules in the brain can “remember” a memory for years, even a lifetime. How it is that our brain’s cells can permanently store information that we learn?    Researchers at the Stowers Institute of Medical Research reveals that prion like protein may participate in persistence of  memory in eukaryotes.  The research led  by Kausik Si of Stowers Institute for Medical Research and Nobel laureate Eric Kandel suggest that prions may be the best solution to the problem.  Prions marked the ability to assume two distinct conformational states – one is dominant and self perpetuating. Once a protein switches to prion state it has the ability to convert other non prion proteins to that state. Thus once engaged the prion state, it continues to be self-renewing and stable.  The study concludes that memory traces may depend on a fairly unique mechanism involving a prion-like protein known as CPEB.  CPEB (cytoplasmic polyadenylation element binding protein) was involved in memory formation in the sea slug Aplysia.

Sea slug Aplysia

Scientists now know that long-term memories are encoded in the synapses between neurons. A unique pattern of synapses is activated in your brain when you remember the street you lived on in first grade; a different pattern is activated when you think of the taste of your favorite food. In order to store one of these memories, existing synapses are strengthened and new synapses are formed.  Now it is known that plenty of that plenty of prion-like proteins are found in relatively simple organisms such as yeast, some of which have known functions.  According to a report in Cell suggest that the prion in yeast may serve as an important source of variation in nature.Si’s team made its discovery in studies of the sea slug Aplysia.

The sea slug serves as a model organism for learning and memory for decades. While studying the CPEB protein in Aplysia, the researchers noticed something unusual about its sequence of amino acids, the building blocks of the protein. CPEB’s amino acid sequence looked suspiciously like sequences typical in prion proteins. Prion-like proteins can naturally occur in an organism, and are not always poisonous, but because of their unusual shapes, they almost never perform a useful function.

According to some early reports, the researchers inserted the Aplysia CPEB protein into yeast cells, to see if the CPEB protein did indeed behaviour like a prion. (because direct observations are easier in simple organisms such as yeast than in animals such as Aplysia), and looked for prion-like behavior. What they found confirmed their hunch: CPEB proteins developed into two different forms, a regular protein and a misshapen one. Typical of prion behavior, when a normally shaped CPEB protein encountered a prion counterpart, it too turned into a prion. “Persistence of memory is a difficult problem,” Si said. The new fact offers “at least an idea” for how this may happen and he suspects the prion-like protein’s apparent role in memory may turn out to be a more general phenomenon. His group is following up on their findings by investigating the role of the fly version of CPEB, and Si added that humans do have a similar protein.

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