Navigation Links
Researchers identify proteins that might contribute to memory loss and Alzheimer's disease
Date:1/15/2010

PHOENIX, Ariz. Jan. 15, 2009 A scientific group led by the Translational Genomics Research Institute (TGen) have identified three kinases, or proteins, that dismantle connections within brain cells, which may lead to memory loss associated with Alzheimer's disease.

These findings, the results of a multi-year TGen study, are published in this month's edition of BMC Genomics in a paper titled: High-content siRNA screening of the kinome identifies kinases involved in Alzheimer's disease-related tau hyperphosphorylation.

The three kinases were found to cause a malfunction in tau, a protein critical to the formation of the microtubule bridges within brain cells, or neurons. These bridges support the synaptic connections that, like computer circuits, allow neurons to communicate with each other.

"The ultimate result of tau dysfunction is that neurons lose their connections to other neurons, and when neurons are no longer communicating, that has profound effects on cognition the ability to think and reason,'' said Dr. Travis Dunckley, an Associate Investigator in TGen's Neurodegenerative Research Unit and the scientific paper's senior author.

Tau performs a critical role in the brain by helping bind together microtubules, which are sub-cellular structures that create scaffolding in the neurons, allowing them to stretch out along bridges called axons. The axons support the synaptic, or chemical, connections with other neurons.

Under normal circumstances, kinases regulate tau by adding phosphates. This process, called tau phosphorylation, enables the microtubules to unbind and then bind again, allowing brain cells to connect and reconnect with other brain cells.

"That facilitates synaptic plasticity. It facilitates the ability of people to form new memories to form new connections between different neurons and maintain those memories. So, it's an essential function,'' Dr. Dunckley said.

However, sometimes the tau protein becomes hyperphosphorylated, a condition in which the tau creates neurofibrillary tangles, one of the signature indicators of Alzheimer's.

"When tau protein is hyperphosphorylated, the microtubule comes apart basically destroying that bridge and the neurons can no longer communicate with each other,'' Dr. Dunckley said.

TGen investigators created sophisticated tests to look at all 572 known and theoretical kinases within human cells. They identified 26 associated with the phosphorylation of tau. Of these 26, three of them EIF2AK2, DYRK1A and AKAP13 were found to cause hyperphosphorylation of tau, permanently dismantling the microtubule bridges.

"This paper shows, for the first time, these three kinases affect Alzheimer's disease-relevant tau hyperphosphorylation, in which most of the tau protein is now driven into a permanently phosphorylated form,'' Dr. Dunckley said.

Dr. Eric Reiman, clinical director of TGen's Neurogenomics Division and executive director of the Banner Alzheimer's Institute, explained that tau holds together the skeleton inside neurons. When phosphate molecules stick to tau proteins, the skeleton falls apart and the neurons begin to retract their synaptic branches and die, leading to memory loss and thinking problems.

In this study, researchers used a molecular tool called siRNA to screen the entire human genome, said Dr. Reiman, a co-author of the scientific paper. This tool enabled the TGen-led team to discover which proteins, when genetically turned off, prevent phosphate molecules from sticking to tau. The three kinases, or proteins, that appear to contribute to the formation of brain tangles, can now be targeted by protein-inhibitor drugs.

"This study used a powerful tool to discover three proteins that may be involved in tangle formation. If safe and well-tolerated tangle-busting medications can be developed, they offer great promise in the treatment of Alzheimer's disease,'' said Dr. Reiman, who also is Director of the Arizona Alzheimer's Consortium.

The next step will be to identify drug compounds that can negate the effects of the three kinases linked to tau hyperphosphorylation.

"The reason that we did this study was to identify therapeutic targets for Alzheimer's disease, whereby we could modify the progression of tau pathology,'' Dr. Dunckley said. "This was a screen to identify what the relevant targets are. Now, we want to match those targets to treatments.''


'/>"/>

Contact: Steve Yozwiak
syozwiak@tgen.org
602-343-8704
The Translational Genomics Research Institute
Source:Eurekalert

Related biology news :

1. University of Pittsburgh researchers launching trial of new osteoporosis drug
2. TGen-Scottsdale Healthcare researchers make breakthrough in lung cancer
3. Researchers discover genetic differences between lethal and treatable forms of leukemia
4. U of Alberta researchers find mechanism that could prevent or treat deadly peroxisome diseases
5. Researchers pin down long-elusive protein thats essential to life as we know it
6. Researchers use new acoustic tools to study marine mammals and fish
7. Researchers to investigate the genetics of congenital heart disease
8. Researchers design a tool to induce controlled suicide in human cells
9. Researchers work on vaccine to improve immune system in newborns
10. IUPUI researchers tackle protein mechanisms behind limb regeneration
11. MDC researchers identify a scaffold regulating protein disposal
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/13/2017)... 2017 Former 9/11 Commission border counsel and ... Janice Kephart of Identity Strategy Partners, LLP, today ... "Executive Order: Protecting the Nation From Foreign Terrorist ... "As President Trump,s ,Travel Ban, Executive Order gains ... banned the travel ban, it is important that our ...
(Date:2/8/2017)... 7, 2017  Aware, Inc. (NASDAQ: AWRE ), ... financial results for its quarter and year ended December 31, ... 2016 was $3.9 million compared to $6.9 million in the ... of 2016 was $0.6 million compared to $2.6 million in ... quarter of 2016 was $0.5 million, or $0.02 per diluted ...
(Date:2/7/2017)... , Feb. 7, 2017   MedNet Solutions , ... entire spectrum of clinical research, is pleased to announce ... , its innovative, highly flexible and award winning eClinical ... customers. iMedNet is a proven Software-as-a-Service (SaaS) ... Data Capture (EDC), but also delivers an entire suite ...
Breaking Biology News(10 mins):
(Date:2/23/2017)...  Capricor Therapeutics, Inc. (NASDAQ: CAPR), a biotechnology company developing ... that Linda Marbán, Ph.D, president and chief executive officer, is ... Cowen and Company 37th Annual Health Care Conference ... Boston, MA 29th Annual ROTH ... pm ET) Dana Point, CA ...
(Date:2/23/2017)... CARDIFF, UK (PRWEB) , ... February 22, 2017 ... ... for optics and photonics , have been named Fellows of the Society this ... and technical contributions in the multidisciplinary fields of optics, photonics, and imaging as ...
(Date:2/22/2017)... ... February 22, 2017 , ... Park Systems , ... AFM Luncheon for all SPIE attendees and Park customers on Feb. ... block from the San Jose Convention Center. The luncheon will feature a talk ...
(Date:2/22/2017)... Washington, PA (PRWEB) , ... ... ... Omnia-Prova Education Collaborative (TOPEC), the leading medical education provider of women’s ... with Commendation by the Accreditation Council for Continuing Medical Education (ACCME). ACCME’s ...
Breaking Biology Technology: