University of California, Santa Barbara (UCSB)

The Pathobiology of Tau Inclusions

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One of the most important cellular facets of memory encoding occurs at synapses. A very important part of learning is strengthening synapses and part of strengthening a synapse involves making new proteins. The production of new proteins can only occur when the RNA that will make the required proteins is turned on. Until then, the RNA is “locked up” by a silencing molecule, which is a micro-RNA. The RNA and micro-RNA are part of a package that includes several other proteins. When a synapse is activated one of the proteins in this package degrades and the silencing complex is no longer silent. The RNA, which is located right next to the synapses begins to make a protein and that protein contributes to strengthening the synapse.

Scientists have been perplexed for some time as to why, when synapses are strengthened, you need to have proteins degrade and also make new proteins. Protein degradation going on side by side with the synthesis of new proteins seemed paradoxical. We have shown that protein degradation is what releases the synthetic machinery to make new proteins. The newly synthesized proteins are a very specific set that control synaptic strength. One set of proteins controlled in this manner are the enzymes that add or remove a palmitate to synaptic proteins. Palmitate is a lipid that attaches to a protein and results in changes in the shape of synapses.