Navigation Links
Study identifies protein that contributes to cognitive decline in Alzheimer's
Date:6/25/2013

NEW YORK, NY (June 25, 2013) Researchers at Columbia University Medical Center (CUMC) have demonstrated that a protein called caspase-2 is a key regulator of a signaling pathway that leads to cognitive decline in Alzheimer's disease. The findings, made in a mouse model of Alzheimer's, suggest that inhibiting this protein could prevent the neuronal damage and subsequent cognitive decline associated with the disease. The study was published this month in the online journal Nature Communications.

One of the earliest events in Alzheimer's is disruption of the brain's synapses (the small gaps across which nerve impulses are passed), which can lead to neuronal death. Although what drives this process has not been clear, studies have indicated that caspace-2 might be involved, according to senior author Michael Shelanski, MD, PhD, the Delafield Professor of Pathology & Cell Biology, chair of the Department of Pathology & Cell Biology, and co-director of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at CUMC.

Several years ago, in tissue culture studies of mouse neurons, Dr. Shelanski found that caspace-2 plays a critical role in the death of neurons in the presence of amyloid beta, the protein that accumulates in the neurons of people with Alzheimer's. Other researchers have shown that caspase-2 also contributes to the maintenance of normal synaptic functions.

Dr. Shelanski and his team hypothesized that aberrant activation of caspase-2 may cause synaptic changes in Alzheimer's disease. To test this hypothesis, the researchers crossed J20 transgenic mice (a common mouse model of Alzheimer's) with caspase-2 null mice (mice that lack caspase-2). They compared the animals' ability to negotiate a radial-arm water maze, a standard test of cognitive ability, with that of regular J20 mice and of normal mice at 4, 9, and 14 months of age.

The results for the three groups of mice were similar at the first two intervals. At 14 months, however, the J20/caspase-2 null mice did significantly better in the water maze test than the J20 mice and similarly to the normal mice. "We showed that removing caspase-2 from J20 mice prevented memory impairment without significant changes in the level of soluble amyloid beta," said co-lead author Roger Lefort, PhD, associate research scientist at CUMC.

Analysis of the neurons showed that the J20/caspase-2 null mice had a higher density of dendritic spines than the J20 mice. The more spines a neuron has, the more impulses it can transmit.

"The J20/caspase-2 null mice showed the same dendritic spine density and morphology as the normal miceas opposed to the deficits in the J20 mice," said co-lead author Julio Pozueta, PhD. "This strongly suggests that caspase-2 is a critical regulator in the memory decline associated with beta-amyloid in Alzheimer's disease."

The researchers further validated the results in studies of rat neurons in tissue culture.

Finally, the researchers found that caspase-2 interacts with RhoA, a critical regulator of the morphology (form and structure) of dendritic spines. "It appears that in normal neurons, caspase-2 and RhoA form an inactive complex outside the dendritic spines," said Dr. Lefort. "When the complex is exposed to amyloid beta, it breaks apart, activating the two components." Once activated, caspase-2 and RhoA enter the dendritic spines and contribute to their demise, possibly by interacting with a third molecule, the enzyme ROCK-II.

"This raises the possibility that if you can inhibit one or all of these molecules, especially early in the course of Alzheimer's, you might be able to protect neurons and slow down the cognitive effects of the disease," said Dr. Lefort.


'/>"/>

Contact: Karin Eskenazi
ket2116@columbia.edu
212-342-0508
Columbia University Medical Center
Source:Eurekalert

Related biology news :

1. Study by UC Santa Barbara researchers suggests that bacteria communicate by touch
2. Law that regulates shark fishery is too liberal: UBC study
3. New study will help protect vulnerable birds from impacts of climate change
4. Study jointly led by UCSB researcher supports theory of extraterrestrial impact
5. BYU study: Using a gun in bear encounters doesnt make you safer
6. 15-year study: When it comes to creating wetlands, Mother Nature is in charge
7. Pycnogenol (French maritime pine bark extract) shown to improve menopause symptoms in new study
8. Crystal structure of archael chromatin clarified in new study
9. EU-funded study underlines importance of Congo Basin for global climate and biodiversity
10. University of Houston study shows BP oil spill hurt marshes, but recovery possible
11. Study demonstrates cells can acquire new functions through transcriptional regulatory network
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/2/2016)... 2, 2016 Checkpoint Inhibitors for Cancer ... Are you interested in the future of ... checkpoint inhibitors. Visiongain,s report gives those predictions to ... national level. Avoid falling behind in data ... and revenues those emerging cancer therapies can achieve. ...
(Date:2/2/2016)... Feb. 2, 2016   Parabon NanoLabs ... U.S. Army Research Office and the Defense Forensics ... sensitivity of the company,s Snapshot Kinship Inference ... and, more generally, defense-related DNA forensics.  Although Snapshot ... (predicting appearance and ancestry from DNA evidence), it ...
(Date:2/1/2016)... , February 1, 2016 ... advancements to drive global touchfree intuitive gesture control market ... --> Rising sales of consumer electronics coupled with ... control market size through 2020 ... electronics coupled with new technological advancements to drive global ...
Breaking Biology News(10 mins):
(Date:2/9/2016)... ... 2016 , ... Net-Translators, an industry-leading provider of translation, ... and improved website. In an on-going effort to further educate customers and emphasize ... how the company designs and delivers thorough, high-quality results for its growing customer ...
(Date:2/9/2016)... ... February 09, 2016 , ... The American Academy of Thermology ... offering its 2016 AAT Member Certification Qualification Course for Technicians via a two part ... which will include a detailed review of hardware, software, and camera setup/operations, aligns with ...
(Date:2/9/2016)... Feb. 9, 2016  DNAtrix, a clinical ... cancer, announced that its lead product, DNX-2401, ... as an orphan medicinal product for the ... of glioma, strikes approximately 25,000 people a ... http://photos.prnewswire.com/prnh/20160208/330986LOGO --> ...
(Date:2/9/2016)... February 9, 2016 Three-Year Initiative Supports ... to Take Part in Life-Changing Camp ... designed to positively affect the lives of children born with rare ... --> SHPG ) is announcing a new initiative designed to ... well as the future of rare disease care. --> ...
Breaking Biology Technology: