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How Memories Are Made, and Lost

Question: What is the goal of your research? 


Ottavio Arancio: \r\nOkay, the overall goal of the research in my lab is to find a \r\ntherapy\r\nagainst the Alzheimer’s disease. \r\nThat’s a very general way of saying things and to be more \r\nspecific we\r\nare… we have different strategies in the lab to go to achieve this goal,\r\n so we\r\nare trying to approach it from different perspectives and if I have to\r\nsummarize these perspectives in a few words I should say that in one \r\nkind of\r\nstudies we are trying to understand what is the function of a molecule \r\nthat is\r\ncalled beta amyloid and this is a molecule made by many amino acids.  Once there are many amino acids\r\ntogether those molecules are called peptides.  Anyway,\r\n this beta amyloid, which is produced in a very high\r\namount in the brain of people with this disease and is known also to be \r\nvery\r\ntoxic to the communication of the cells in the brain and therefore to \r\nlead to\r\nmemory impairment, so but we know that this molecule is present in the \r\nbrain of\r\npeople throughout life, just normal half the people and it is there in \r\nvery low\r\namount and nobody knew what was the function, if at all to any function \r\nthis\r\nprotein in this very low amount. \r\nWhat most of scientists thought was that it was kind of piece of \r\ngarbage\r\nin the brain of people with no relevance whatsoever and instead we have \r\nstarted\r\nworking on it and we have found that actually probably the very likely \r\nfunction\r\nof this protein in very low amount is just to be there to lead to normal\r\nmemory, so without it we cannot store information in the brain, we \r\ncannot learn\r\nand there will not be normal memory. 


So I mean with all the study what we think is that \r\nthis\r\nmolecule is there.  It’s necessary\r\nfor memory and then for some unknown reason we start making…  people with the disease start making a lot\r\nof it and the fact there is a lot just makes opposite of what it does in\r\n the\r\nnormal brain, so it’s actually it reduces memory when it is there in a \r\nvery\r\nhigh amount and so this is a very, very you know interesting \r\ncharacteristic and\r\nwe think that actually until the studies were not there what people were\r\n doing\r\nto understand the cause of the disease was just to look at the disease \r\nfrom the\r\nvery end of it instead of trying to understand…  You\r\n know it was a kind of a piece of a puzzle that is\r\nmissing to understand the… to understand how something which is there \r\nbecomes\r\nwhat is the beginning of the end for memory.  So \r\nin other words just to make things more simple because\r\notherwise we get lost here is that now we know that normal function of \r\nthis\r\nprotein in very low amount in the brain is to lead to memories, that \r\nthis\r\nmolecule is necessary for memory and that we now need to understand how \r\nthe\r\nproblem starts, how memory is impaired. \r\nWe need to understand how this normal regulation of the level of \r\nthis\r\nprotein in the brain is broken and so the brain starts to make a lot of\r\nit.  So we think that through this\r\nstudy and through establishing what is normal function of the protein we\r\n could\r\nunderstand at the very beginning of the disease and once you usually \r\nunderstand\r\nhow this starts, which is something which we really do not have it so \r\nfar.


Question: How does this \r\nprotein contribute to\r\nmemory loss?


Ottavio Arancio: What I found is that the normal function \r\nof this protein is\r\nthere to lead to memory, the opposite of memory loss.  So\r\n now I would like to understand the bridge between the\r\nnormal function of this protein, which is just to lead to memory to its\r\nabnormal function, which is the memory loss.  You \r\nsee, so the fact that the protein gives to memory loss\r\nis something that was already known by scientists.  It’s\r\n slightly different.  I don’t want to take credit \r\nof something I did not\r\ndiscover.  What I have discovered\r\nis that this protein in normal low concentration leads to memory.  It leads to memory loss the opposite\r\nonly when it is there in very high amount, and I would like to bridge \r\nthe gap\r\nbetween its normal function and its pathological function, its bad\r\nfunction.  How does a good turn\r\ninto a bad guy?  How does a good\r\nprotein turn into a bad protein?

A protein that scientists once thought was a "piece of garbage in the brain" turns out to play a key role in memory formation. At high concentrations, however, it spells "the beginning of the end for memory."

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