Navigation Links
Impaired energy metabolism linked with initiation of plaques in Alzheimer's brain
Date:12/24/2008

Scientists have identified an initiating molecular mechanism in sporadic Alzheimer's disease (AD). The study, published by Cell Press in the December 26th issue of the journal Neuron, provides new information about generation of damaging amyloid β (Aβ) plaques within the AD brain and underscores the importance of developing new preventative and disease-modifying therapies for AD, especially those aimed at interrupting pathological Aβ-production.

AD, the leading cause of dementia in the elderly, is a devastating neurological disorder characterized by accumulation and deposition of sticky clumps of A? protein. A? protein is generated from amyloid precursor protein (APP) by ?-site APP cleaving enzyme (BACE1). Previous research has suggested that BACE1 activity may play a key role in the initiation of AD pathogenesis and identified BACE1 as a promising target for AD therapeutics.

Recently, BACE1 was linked to cellular stress responses in the brain. Importantly, the AD brain exhibits impaired energy metabolism (a stressful situation) and it has been suggested that diminished cerebral use of glucose and oxygen may be an early event in AD pathogenesis.

Senior study author Dr. Robert Vassar from Northwestern University Feinberg School of Medicine has explored the link between energy inhibition and AD pathogenesis. "We have shown previously, using a pharmacological model of energy metabolism inhibition in pre-plaque transgenic mice with an excess of APP, that BACE1 and Aβ levels are elevated in the brain," says Dr. Vassar.

Dr. Vassar and colleagues expanded on their previous work by using glucose deprivation to examine the molecular mechanisms underlying elevated BACE1 levels in response to energy inhibition. They found that glucose deprivation caused an increase in BACE1 levels and led to the phosphorylation of the stress-inducible translation initiation factor, eIF2?. Further, direct phosphorylation of eIF2? increased BACE1 levels and enhanced Aβ production while inhibition of eIF2? phosphorylation prevented energy-deprivation induced increases in BACE1.

The researchers went on to show that energy inhibition increased eIF2? phosphorylation, BACE1 levels and amyloid plaque formation in APP transgenic mice. In addition, phosphorylated eIF2? and BACE1 were elevated in an aggressive A? plaque-forming mouse model and in humans with AD.

"Here, for the first time we provide evidence linking impaired energy metabolism, an AD-relevant stress, with BACE1 translation mediated by eIF2? phosphorylation," says Dr. Vassar. "Our findings implicate phosphorylated eIF2? in both the initiation and progression of sporadic AD. Future experiments will determine whether inhibition of eIF2? phosphorylation could be an efficacious therapeutic approach for the prevention and treatment of AD."


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related biology news :

1. Scientists identify cell changes leading to impaired artificial kidney function
2. Telescope embedded in glasses lens promises to make driving easier for visually impaired
3. New research program for energy innovations
4. Turning over a new leaf for future energy supplies
5. World Energy Outlook to be presented at Rice University Dec. 9
6. New publishing partnership for Energy for Sustainable Development
7. Fish technology draws renewable energy from slow water currents
8. A model to measure soil health in the era of bioenergy
9. Energy Biosciences Institue named "Deal of Distinction" by tech-transfer group
10. Scientific community called upon to resolve debate on net energy once and for all
11. Trustee makes donation to start new solar energy research center at Rensselaer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/3/2016)... , Feb. 3, 2016 Vigilant Solutions ... Police Department in Missouri solved ... plate reader (LPR) data from Vigilant Solutions. ... case in which the victim was walking out of a convenience store and ... space next to his vehicle, striking his vehicle and ...
(Date:2/2/2016)... Feb. 2, 2016 Technology Enhancements Accelerate Growth of ... of the digital and computed radiography markets in ... and Indonesia (TIM). It provides ... size, as well as regional market drivers and restraints. ... market penetration and market attractiveness, both for digital and ...
(Date:2/1/2016)... ( www.wocketwallet.com ) announces the launch of a new video featuring singer, ... Las Vegas , where Joey appeared at the Wocket booth to ... , where Joey appeared at the Wocket booth to meet and greet ... the Consumer Electronics Show (CES2016) in Las Vegas , ... --> --> The video is ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... 2016  Neurocrine Biosciences, Inc. (NASDAQ: NBIX ) today announced ... 2015. --> --> For ... of $29.3 million, or $0.34 loss per share, compared to a ... the same period in 2014. For the year ended December 31, ... $1.05 loss per share, as compared to a net loss of ...
(Date:2/11/2016)... , Feb. 11, 2016  Wellcentive today ... Portland, Oregon -based community care ... provide population health analytics, quality reporting and care ... FamilyCare strengthen its team of quality managers, analysts ... to the provider groups serving FamilyCare members. ...
(Date:2/11/2016)... York (PRWEB) , ... February 11, 2016 , ... ... instruments for more than 150 years, continues today to pursue the highest level ... line of analytical instruments: the AR9 Refractometer and the AR5 Refractometer. Accurate, ...
(Date:2/10/2016)... , Feb. 10, 2016  The Maryland House of ... has announced that University of Maryland School of Medicine ... and University of Maryland Medical System President and CEO ... "Speaker,s Medallion," the highest honor given to the public ... Dean Reece and Mr. Chrencik for ...
Breaking Biology Technology: