Featured Research

from universities, journals, and other organizations

Protein Inhibitor Helps Rid Brain Of Toxic Tau Protein

Date:
September 30, 2009
Source:
University of South Florida Health
Summary:
Inhibiting the protein Hsp70 rapidly reduces brain levels of tau, a protein associated with Alzheimer's disease when it accumulates as memory-choking tangles. One of the more effective Hsp70-inhibitor drugs was a derivative of methylthioninium chloride, or Rember, a new laboratory study by neuroscientists found.

Inhibiting the protein Hsp70 rapidly reduces brain levels of tau, a protein associated with Alzheimer's disease when it builds up abnormally inside nerve cells affecting memory, neuroscientists at the University of South Florida found. The study is reported online September 29 in the Journal of Neuroscience.

"Now that we've discovered that targeting the chaperone protein Hsp70 can clear tau, it could be helpful in finding more effective drugs for Alzheimer's disease," said the study's senior author Chad Dickey, PhD, assistant professor of molecular medicine who works out of the Byrd Alzheimer's Institute at USF Health "The therapeutic strategy may also be applicable to other neurodegenerative diseases involving Hsp70, such as Huntington disease, amyotrophic lateral sclerosis (ALS), and some cancers."

Hsp70 is a one of several "chaperone" proteins that supervises the activity of tau inside nerve cells. The normal function of tau is to support the structure of nerve cells, much like the skeleton provides a scaffold to support the body. Tau is inside nerve cells, while another hallmark protein associated with Alzheimer's, beta amyloid, is outside the neurons.

Working with researchers at the University of Michigan, the USF team tested the effects of several compounds on Hsp70 in cell models and brain tissue from mice genetically modified to develop the memory-choking tau tangles. Some compounds activated Hsp70, and others were Hsp70-inhibitors.

One of the more effective Hsp70-inhibitor drugs the researchers discovered was a derivative of methylthioninium chloride, or Rember™, the first experimental medication reported to directly attack the tau tangles in patients with Alzheimer's disease. Rember™ was heralded as a major development in the fight against Alzheimer's when results in early clinical trials were announced last year at the International Conference on Alzheimer's disease.

But Rember™ and its derivatives do have some inherent problems; they're not very potent so effective therapy would require fairly high doses, Dickey said.

"The drug does help prevent the protein (tau) from clumping together, but that in itself doesn't mean it's actively getting rid of the toxic tau," he said. "Now that we know Hsp70 is a target of Rember™, we can develop similarly-acting drugs that will more specifically target this chaperone protein in affected areas of the brain, resulting in fewer side effects."

The USF researchers originally thought activating Hsp70 would direct the chaperone protein to decrease the tau gone bad -- preventing tau from stacking up into tangles inside cells involved in memory and destroying them. But instead of restoring tau to its normal supportive function, activating Hsp70 actually led to tau's preservation and even more accumulation, Dickey said. "Basically we think the chaperone binds to the tau, and somehow in the process of trying to fix things decides to keep holding onto tau when it shouldn't. So, activating Hsp70 is not necessarily what we want to do; we ultimately want to inhibit Hsp70 to promote the release or clearance of tau …to kill the bad tau."

Dr. Dickey emphasizes that problems with Hsp70 alone do not cause Alzheimer's. It likely develops from a convergence of various factors in the brain, he said, including deposits of the other featured Alzheimer's protein beta amyloid, or a genetic defect; disruption of cell signaling; a breakdown in the neuron's support structure, and then accumulation of tau into the memory-choking tangles.

Dr. Dickey's team at USF focuses on how to manipulate with drugs or gene therapy the chaperone proteins that regulate tau's fate – determining whether it's preserved or cleared from the brain. The University of Michigan team works on identifying and developing compounds that may be effective against Alzheimer's disease and other tauopathies.

The study was supported by the national Alzheimer's Association, the National Institute on Aging, the Abe and Irene Pollin Fund for CDB from the Society for Progressive Supranuclear Palsy (CurePSP), and the National Institute of Neurological Disorders and Stroke.

The study's other authors were Umesh Jinwal (lead author), Yoshinari Miyata, John Koren III, Jeffrey Jones, Justin Trotter, Lyra Chang, John O'Leary, David Morgan, Daniel Lee, Cody Shults, Aikaterini Rousaki, Edwin Weeber, Erik Zuiderweg, and Jason Gestwicki.


Story Source:

The above story is based on materials provided by University of South Florida Health. Note: Materials may be edited for content and length.


Cite This Page:

University of South Florida Health. "Protein Inhibitor Helps Rid Brain Of Toxic Tau Protein." ScienceDaily. ScienceDaily, 30 September 2009. <www.sciencedaily.com/releases/2009/09/090929181808.htm>.
University of South Florida Health. (2009, September 30). Protein Inhibitor Helps Rid Brain Of Toxic Tau Protein. ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2009/09/090929181808.htm
University of South Florida Health. "Protein Inhibitor Helps Rid Brain Of Toxic Tau Protein." ScienceDaily. www.sciencedaily.com/releases/2009/09/090929181808.htm (accessed April 18, 2014).

Share This



More Mind & Brain News

Friday, April 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Study On Artists' Brain Shows They're 'Structurally Unique'

Study On Artists' Brain Shows They're 'Structurally Unique'

Newsy (Apr. 17, 2014) The brains of artists aren't really left-brain or right-brain, but rather have extra neural matter in visual and motor control areas. Video provided by Newsy
Powered by NewsLook.com
Is Apathy A Sign Of A Shrinking Brain?

Is Apathy A Sign Of A Shrinking Brain?

Newsy (Apr. 17, 2014) A recent study links apathetic feelings to a smaller brain. Researchers say the results indicate a need for apathy screening for at-risk seniors. Video provided by Newsy
Powered by NewsLook.com
Are School Dress Codes Too Strict?

Are School Dress Codes Too Strict?

AP (Apr. 16, 2014) Pushing the limits on style and self-expression is a rite of passage for teens and even younger kids. How far should schools go with their dress codes? The courts have sided with schools in an era when school safety is paramount. (April 16) Video provided by AP
Powered by NewsLook.com
Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins