The Tau Protein in Neurodegenerative Diseases

 The tau protein is a microtubule-associated protein that is involved in the stabilization of axonal

microtubules and producing polarity in developing neurons. This protein is involved in many

neurodegenerative diseases when it aggregates into tangles called neurofibrillary tangles (NFTs). Some

diseases caused by neurofibrillary tangles of the tau protein include Alzheimer's disease, Parkinson’s

disease, and posttraumatic stress disorders.

The tau protein tangles mainly due to hyperphosphorylation, which causes the tau protein to lose

affinity for microtubules, leading to the destabilization of the microtubules and the loss of integrity of

neurons. Neurons will then have trouble being able to transmit and read signals. Alongside

hyperphosphorylation, abnormal acetylation is also a leading cause of tau proteins not being able to

function as intended. Lysines have been a major site for acetylation and have been evolutionarily

conserved in tau due to their importance in microtubule binding. Abnormal acetylation causes the tau

protein to become dysfunctional and non-degradable, causing them to accumulate and aggregate into

neurofibrillary tangles.

Research has been done on if the aggregation of tau can be transmitted to other organisms. This

was done through the injection of diluted extracts of mutated tau into the brains of mice. This resulted in

the aggregated tau moving from the site of injection to synaptically connected regions through the axons

and dendrites of neurons. This phenomenon is called tau seeding, tau aggregates possess the ability to

recruit and template another tau into misfolding and aggregating as well. This study helped us 

understand the nature of some neurodegenerative diseases caused by tau.

As many neurodegenerative diseases are very common today in our society, countless studies

have been conducted in order to discover treatments for tau-caused neurodegenerative diseases. Many

treatments include the inhibition of phosphorylation in tau. There are kinases that catalyze the

phosphorylation of the tau protein, which would lead to microtubule stability and less tau aggregation.

Acetylation is also a target for these studies, as there are specific residues that are responsible for

acetylating tau. This would stop the creation of non-degradable tau. There is a lot of hope for future

treatments in tau protein-related neurodegenerative diseases, as many of these studies are showing

promising results. I hope that we can see more trustworthy treatment success in the near future.

Sources:

https://www.frontiersin.org/articles/10.3389/fnagi.2019.00204/full#:~:text=The%20main%20role%20of

%20Tau,et%20al.%2C%201995

https://link.springer.com/article/10.1007/s00401-017-1707-9

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099159/#:~:text=As%20described%20above%2C%20ta

u%20is,1B


Victoria Leong (2)

Comments

  1. AnonymousSeptember 27, 2022 at 7:21 PM

    Hi Victoria,
    I find it really interesting how many diseases that we are aware of such as Alzheimer's disease, Parkinson's disease, and PTSD are all caused by the same issue of neurofibrillary tangles of the tau protein. I remember learning about NFTs in one of my biology classes and I thought it was very fascinating to learn what causes them. I'm also curious to see where treatments for tau-caused neurodegenerative diseases go in the future besides inhibiting the phosphorylation of tau.
    Sarah Belcher

    ReplyDelete
  2. Chloe FriarySeptember 28, 2022 at 10:55 AM

    Hi Victoria,
    I find the subject of Tau Proteins very interesting and I remembered learning about it briefly in bio 285. I didn't know the exact process of how the tau protein tangles occurred and how it leads to various diseases so it was very insightful to hear about. I wonder if there are any other similar proteins that lead to neurodegenerative diseases and what their own processes and interactions within the brain look like.

    ReplyDelete
    Replies
    1. Victoria LeongOctober 12, 2022 at 4:22 PM

      Hi Chloe!
      Thanks for your comment! I also remember covering it in Bio 285. I was doing some research on other neurodegenerative diseases to find if there are any similarities as well, which lead me to find a lot of these diseases are related to complex mixture of old age, environmental, factors, and nerve cell impairments. I found it super interesting how there are so many factors that lead towards specific diseases and how similar in nature they are.

      Delete
  3. Owen BradleySeptember 28, 2022 at 3:39 PM

    Hi Victoria,
    I wonder if treatments will be used to treat several different diseases when treatments are finally discovered. It seems like it wasn't that long ago when they didn't even know the cause of some of these diseases, now treatment may start appearing in the near future. It's nice that people will finally receive treatment, these illnesses are so horrible. No one should experience them.

    ReplyDelete
    Replies
    1. Victoria LeongOctober 12, 2022 at 4:15 PM

      Hi Owen!
      Thank you for your comment! I agree that these diseases are very horrible, which makes me want to know more about if there are any conclusive research done towards a successful treatment. But sadly, as of now, I haven't seen any conclusive treatments. There are some clinical trials that look promising. The more research we do into these diseases, the more we understand how they work. Hopefully, we can see some more promising results in the future!

      Delete
  4. AnonymousSeptember 28, 2022 at 5:05 PM

    Hi Victoria,
    I remember tau being mentioned slightly in my biology classes, and I always wanted to learn more about it. Do you know if there has been any clinical trials for neurodegenerative diseases that uses any of this gained information about tau, like acetylating tau, as a way to treat the disease?

    ReplyDelete
    Replies
    1. AnonymousSeptember 28, 2022 at 5:05 PM

      - Tiffany Pham

      Delete
    2. Victoria LeongOctober 12, 2022 at 4:10 PM

      Hi Tiffany!
      Thank you for your comment. I haven't seen any conclusive clinical trials yet, but there is one trial in particular that I read more about, called the DIAN-TU trail. This clinical trial has three branches that focus on targeting the amyloid plaques. The particular branch that is ongoing today looks at the antibody that recognizes and binds to the MBTR region of the tau protein. The next branches are set to launch in later 2022 and 2023. I really hope to see some conclusive evidence in the future.

      Delete

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