A scientific journal PLOS Biology published a study that says prion-like proteins aren’t involved in disease processes only. They are crucial for creating and maintaining long-term memories as well. The research was conducted by experts at the Stowers Institute for Medical Research. The scientists reveal that these prion-like proteins can be precisely controlled so that they are produced only in a specific time and place.
It is a general concept that prions are notoriously destructive. They are spurring proteins that misfold and interfere with cellular function as they spread without control. However, this study reveals another side of these proteins that they are important for memory to persist. The protein must be tightly regulated to ensure that long-lasting memories are created only in the appropriate neural circuits. This tight regulation of the protein causes it to adopt its prion-like form only in response to specific stimuli.
The research focuses on finding the molecular modifications that encode memory in specific neurons. This research points toward prion-like proteins as vital regulators of long-term memory.
The experts demonstrated that the formation of prion in nerve cells is significant for the perseverance of long-term memory in fruit flies. This is because the conversion of prions is self-sustaining. Once a prion-forming protein has shifted into its prion shape, additional proteins continue to convert without any additional stimulus.
Fruit flies were found to have the Orb2 protein necessary for memories to persist. It is a prion-forming protein. Flies producing a mutated version of Orb2 learn new behaviors but have short-lived memories. Their memories are unstable initially whereas, they disappear completely by three days.
How do memories form at the right time?
The researchers aimed at investigating how prion formation and regulation could be controlled so that memories form at the right time. They believe that prion-formation being the biochemical basis of memory must be regulated. However, prion formation appears to be random for all the cases known so far.
Orb2 protein has two forms,
The latter is widespread throughout the fruit fly’s nervous system. On the other hand, Orb2A appears only in a few neurons, at extremely low concentrations. Moreover, Orb2A quickly falls apart because its half-life is only an hour long.
Orb2A acts as a seed to trigger the conversion of the protein to the prion state. As mentioned above, the conversion is a self-sustaining process. Additional Orb2 continues to convert to the prion state, with or without Orb2A. If the abundance of the Orb2A seed is altered, cells might regulate where, when, and how the conversion process is engaged.
When a protein called TOB associates with Orb2A, it becomes much more stable and its half-life increases to 24 hours. This step might raise the frequency of the prion-like state and explain how the conversion of Orb2 to the prion state can be restricted in both time and space.
The findings of the study raise a question that what happens when Orb2 enters its prion-like state, as well as where in the brain the process occurs. The scientists are putting continuous efforts to answer these potential questions and enumerate the hidden parameters.