Navigation Links
How neuronal activity leads to Alzheimer's protein cleavage
Date:10/19/2008

Amyloid precursor protein (APP), whose cleavage product, amyloid-b (Ab), builds up into fibrous plaques in the brains of Alzheimer's disease patients, jumps from one specialized membrane microdomain to another to be cleaved, report Sakurai et al.

Although there is no definitive evidence that Ab plaques are the direct cause of Alzheimer's disease, there is much circumstantial evidence to support this. And working on this hypothesis, scientists are investigating just how the plaques form and what might be done to stop or reverse their formation.

APP, a protein of unknown function, is membrane associated and concentrates at the neuronal synapse. Certain factors such as high cellular cholesterol and increased neuronal or synaptic activity are known to drive APP cleavage, and Sakurai and colleagues' paper pulls these two modes of Ab regulation together.

APP associates with membrane microdomains high in cholesterols (lipid rafts). These lipid rafts can also contain the enzyme necessary for APP cleavage, BACE. Synaptic activity is known to involve a very different type of membrane microdomain high in an excytosis-promoting factor called syntaxin. Sakurai et al. now show that although APP preferentially associates with syntaxin microdomains, upon neuronal stimulation APP instead associates with microdomains that contain BACE.

It's unclear why APP should be associated with syntaxin, though it might suggest a role for APP in vesicle trafficking and exocytosis. Also unclear is why neuronal activity should cause APP to jump from syntaxin domains to BACE domains. What is clear, however, is that the process is an active one, requiring a kinase called cdk5. Furthermore, treating neurons with a cdk5 inhibitor called roscovitine, which is currently in trials for cancer treatment, reduced APP's association with BACE microdomains and reduced APP cleavage.


'/>"/>

Contact: Sati Motieram
motierd@mail.rockefeller.edu
212-327-8581
Rockefeller University Press
Source:Eurekalert

Page: 1

Related biology news :

1. Researchers uncover mechanism of action of antibiotic able to reduce neuronal cell death in brain
2. Neuronal circuits able to rewire on the fly to sharpen senses
3. Neuronal conduction of excitation without action potentials based on ceramide production
4. Carnegie Mellon scientists investigate initial molecular mechanism that triggers neuronal firing
5. Guidelines urge physical activity during pregnancy
6. Radioactivity: Discover the lowest amounts with new methods
7. PTC124 shows activity in cystic fibrosis; Phase 2 proof-of-concept data published in Lancet
8. Study finds connections between genetics, brain activity and preference
9. Pitt receives $2.5 million to simulate and analyze brain, immune system activity
10. Eribulin mesylate demonstrated anti-tumor activity in patients with advanced breast cancer
11. UM coral scientist Peter Glynn wins award for scholarly activity
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/23/2017)... Aug. 23, 2017  The general public,s help is being enlisted in ... that live in and on the human body –and are believed to ... The Microbiome Immunity Project ... microbiome, starting with the gut. The project's goal is to help advance ... IBM ...
(Date:8/15/2017)... --  ivWatch LLC , a medical device company focused on improving ... of its ISO 13485 Certification, the global standard for medical device ... (ISO®). ... Monitoring device for the early detection of IV infiltrations. ... "This is an important milestone for ivWatch, as it ...
(Date:7/20/2017)... (NYSE: DAL ) customers now can use fingerprints instead of ... Airport (DCA). ... Delta launches biometrics to board aircraft at Reagan Washington National Airport ... Delta,s biometric boarding pass experience that launched in May ... boarding process to allow eligible Delta SkyMiles Members who are enrolled in ...
Breaking Biology News(10 mins):
(Date:9/26/2017)... ... ... “The American Academy of Anti-Aging and Preventative Medicine declares War on Dementia,” proclaimed ... Die with a form of Dementia. , The 28,000 Physicians and Scientists of ... potential to slow and reverse Dementia and brain aging. , If you think 1/3 ...
(Date:9/26/2017)... Kent, WA (PRWEB) , ... September 26, 2017 ... ... assembled Pilot Skid membrane filtration systems. , These Pilot Skid Systems are specifically ... processes. They offer more than 200 times the filtration surface available in standard ...
(Date:9/26/2017)... ... 2017 , ... arivis, Inc., a provider of clinical and ... Shield EU-US. This milestone assures clients using arivis Clireo technologies that their data ... arivis clients can more assuredly operate their clinical and regulatory processes within Clireo, ...
(Date:9/25/2017)... ... 25, 2017 , ... eClinical Solutions LLC, an industry-leading provider ... announced today that the elluminate® Data Intelligence Hub has been selected as ... NextGen Technology Innovation Awards . , elluminate is a cloud based ...
Breaking Biology Technology: