Developing new drugs for Alzheimer’s Disease: Targeting misfolded proteins

The search for new drugs

When scientists search for new drugs, they begin by looking at the disease or disorder in question. If the cause of a disorder is known, research focuses on attempting to eliminate it. But if that doesn’t work, or if a scientist is studying a disease like Alzheimer’s, where the cause is not known, then she begins to look at the major problems or symptoms of the disease. Three of the major problems in Alzheimer’s disease are 1) synapses that don’t work properly, 2) neurons that lack the energy they need to function, and 3) misfolding of specific proteins.

Two weeks ago, I wrote about the synapses and drugs that directly affect synaptic transmission. To see that post, click here. Last week, the topic was the energy deficit in Alzheimer neurons, and the search for drugs that enhance mitochondrial function. You can read about that here.

Today, I want to begin talking about the misfolded proteins of Alzheimer’s disease. It’s a complicated topic, so we’re going to approach it bit by bit. First, we need some background information:

For proteins, folding properly is a big deal

When your cells make proteins, they connect protein subunits (called amino acids) together like beads on a string. There are twenty common subunits, each with a different 3-D shape. The subunits used and the order in which they are strung determines many of the traits of the protein made.

Now this is the part that is important to understand… The function of a protein depends on its three-dimensional shape.

When proteins are being made, there is an entire class of helper proteins (called chaperones) who have the important job of making sure the new proteins get folded into their proper functional shapes. (Yes, “who.” I fully intend to talk about proteins as if they were people. Grammarians will just have to deal with it.)

But proteins don’t always stay neatly folded. Changes in temperature, changes in acidity, even interactions with other molecules can cause proteins to change their shape.

If a protein unfolds completely and stays that way, it is essentially dead and cannot perform its function in the cell. (This is, quite literally, what happens when you cook an egg. Egg white is a protein called ovalbumin, and when it is unfolded, it goes from being clear and runny to being white and stiff.) Though we eat and digest many denatured proteins, allowing the subunits they are made of to be recycled, within the cell, proteins that are even partially unfolded are essentially useless.

Normally, unfolded or misfolded proteins are degraded and destroyed by the clean-up organelles of the cell.

In Alzheimer’s disease, misfolded proteins persist

However, in Alzheimer’s disease, beta-amyloid protein and the protein tau adopt abnormal misfolded shapes, and the cell is unable to degrade them properly.  Beta-amyloid is the main component of the senile plaques found in Alzheimer brain. Tau protein produces tangles inside the neurons.

Both beta-amyloid protein and tau protein are targeted by drug developers. In future posts, I’ll write about the approaches being used to fight their deposition in brain.

If you have questions or comments, please respond below.

If you would like to follow this blog by email, sign up in the box, upper right.

If you’d prefer some lighter reading, try my Transitions blog.

Wishing you the best,

–Susan.

Advertisements

3 thoughts on “Developing new drugs for Alzheimer’s Disease: Targeting misfolded proteins

  1. Susan, I am following your Alzheimer’s posts with great interest. My mom is struggling with this disease–well, actually, I think it’s my dad who is doing the most struggling with her disease. I had no idea about the folding and unfolding of proteins. Looking forward to your next post about it.

    Like

    • Jlynn, my heart goes out to your family. Alzheimer’s is a devastating disease. If your dad is looking for encouragement as a caregiver for your mom, you might want to look also at the Alzheimer’s Reading Room. It is primarily about day to day with Alzheimer’s, written by Bob DeMarco who has been caring for his mother for many years. I’d give you the link, but I am on a brand new computer–my first Apple in 30 years–and I haven’t yet figured out how to open another window in order to go copy the Alz. Room link. You’ll find it with Google. See if you think it might be helpful to your dad.
      I am so glad you find the posts interesting. I believe it helps to understand what is actually happening in the brain. I sincerely hope you find that to be true. Best wishes, –Susan.

      Like

  2. Pingback: Misfolded Proteins of Alzheimer’s Disease: Tau Protein | by Susan Craig Ideas, Information, Insight

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s