Understanding the Role of Polyamines During Taupathies
Daniel Lee, PhD, University of South Florida, Tampa
- Tau Filaments
- Stabilizes structures called microtubules which support neuronal function
- Tau can misfold, fall off of microtubules, and can clump or aggregate that are hard for the cell to digest
- Tau therapies approaches include trying to stabilize and trying to decrease clumping
- Polyamines Increase protein clearance, regulate genes, promote cell growth, and regulate neuronal activity and stability
- What are polyamines?
- We get them from plants and fruits, and our body synthesizes them as well
- Goes through a process that makes little molecules (polyamines)
- Our body has a very good way of regulating these levels of polyamines.
- Converts it to an inactive form and can either be removed from the cell, or be recycled back in the body
- Often times, there’s an excess of these inactive tau products
- Trying to understand why this is happening…
- How can we decrease the amount of inactive tau and boost amount of active
- Tau Aggregation Assay
- Microtubule Polymerization Assay
- When you add polyamines to the system, you decrease the clumping
- If you add inactive products, you promote more tau clumping
- Polyamines decrease tau aggregation and promote microtubule
- SRM-Gene therapy –memory recall
- Make proteins and overexpress the enzymes that promote production of tau
- Tested on mice, inject right into the brain, testing memory
- Mice with tau learn much slower than mice with boosted polyamines
- Leads us to think that we need to boost polyamines
- Make proteins and overexpress the enzymes that promote production of tau
- Using in vivo microdialysis to measure tau
- Samples the environment of the brain, so we’re able to see what’s in there
- Can get real time measurements of how tau is moving in the brain
- During activity they are being released, and that doesn’t seem to be a good thing
- Can be used as a good therapeutic for future targets