Navigation Links
Collagen VI may help protect the brain against Alzheimer's disease
Date:1/5/2009

SAN FRANCISCO, CA January 5, 2008 Scientists from the Gladstone Institute of Neurological Disease (GIND), UCSF, and Stanford have discovered that a certain type of collagen, collagen VI, protects brain cells against amyloid-beta (Aβ) proteins, which are widely thought to cause Alzheimer's disease (AD). While the functions of collagens in cartilage and muscle are well established, before this study it was unknown that collagen VI is made by neurons in the brain and that it can fulfill important neuroprotective functions.

The team of investigators led by GIND director Lennart Mucke, MD, reported in the current edition of the journal Nature Neuroscience, that collagen VI is increased in brain tissues of Alzheimer's patients.

"We first noticed the increase in collagen VI in the brain of AD mouse models, which inspired us to look for it in the human condition and to define its role in the disease," said Dr. Mucke.

The Gladstone team had profiled changes in gene expression using DNA microarrays, which provides an unbiased method for identifying key biological pathways. By comparing all of the genes that are active in disease and normal tissue, one can get valuable information on new pathways and potential therapeutic targets.

The researchers looked at the dentate gyrus, a specific area of the brain that is critical to memory and particularly vulnerable in AD, and compared the genes that were turned on and off in normal mice and a mouse model of AD. This analysis revealed the striking increase in collagen VI in the brains of mice that model AD.

Building on this initial finding, the team examined brain tissue from AD patients and normal non-demented humans and found that collagen VI expression was also higher in the AD patients. They further discovered that the cellular source of the collagen VI in the brain was neurons, the very cells that the disease attacks and that we all need to think and remember.

"These findings were really surprising and exciting to us because nobody knew anything about collagen VI in the brain," said Jason Cheng, MD, co-lead author of the study. "We were particularly curious whether collagen VI contributed to neuronal damage in AD or was produced as a defense mechanism against it," added Dena Dubal, MD, PhD, co-lead author of the study.

To answer this and other questions, the scientists carried out a series of informative cell culture experiments. These experiments revealed found that Aβ added to neurons grown in culture increased the expression of collagen VI and that this process involved the immune regulatory cytokine TGFβ. What is more, the team discovered that increasing the amount of collagen VI in the cultures effectively protected the neurons against Aβ toxicity.

"This striking protective effect suggests that increased neuronal production of collagen VI is an important component of the brain's defense against Aβ," said Dr. Mucke. "It made us really curious about the underlying mechanisms."

To clinch these mechanisms, Dr. Mucke's team examined the direct interactions of collagen VI with Aβ. They looked at how Aβ attacks individual neurons in cell culture. Small poisonous Aβ assemblies, called oligomers, bind strongly to vulnerable neurons in the brain, but in the presence of collagen VI, this binding was blocked. Using immunohistochemistry and atomic force microscopy, they showed that collagen VI and Aβ form large aggregates with each other that may sequester the smaller, more toxic Aβ complexes away from neurons.

"We are eager to explore how this kind of process might be enhanced therapeutically and how we can best leverage it for the development of more effective treatments for this devastating condition," said Dr. Dubal.


'/>"/>

Contact: Valerie Tucker
vtucker@gladstone.ucsf.edu
415-734-2019
Gladstone Institutes
Source:Eurekalert

Related medicine news :

1. New Injectable Collagen Filler Offers Natural Results
2. Galderma Completes Tender Offer for CollaGenex
3. Galderma Announces HSR Clearance for Its Proposal to Acquire CollaGenex Pharmaceuticals
4. Galderma Reaches Agreement to Acquire CollaGenex Pharmaceuticals
5. AGI Dermatics Data Indicates 8 Oxo-Guanine Repair Enzyme OGG1 Encapsulated in Liposomes, Reduces MMP-1, Increases Collagen and Enhances DNA Repair
6. Collagen Matrix, Inc. Receives FDA 510(k) Clearance for SynOss(TM) Synthetic Mineral Bone Graft Material
7. Prenatal Nutrition, Postnatal Allergy Protection
8. To Protect Yourself, Wash Those Germs Away
9. What are protective effects of anti-ricin A-chain aptamer?
10. Exercise Protects Black Women From Type 2 Diabetes
11. Facing Deadly Ice Storms, Home Medical Equipment Providers in New England Mobilize to Protect Oxygen Patients
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/20/2017)... , ... January 20, 2017 , ... Source Vitál Apothecary, ... 100 percent pure essential oils, announced the company had a successful visit to the ... annual ECRM event gives companies that work in the nutritional, sports and health industries ...
(Date:1/20/2017)... ... January 20, 2017 , ... ATP Science, ... everyday lives, recently attended the January ECRM Trade Show in Hilton Head, SC, ... for its large range of supplements that keep the body functioning at its ...
(Date:1/20/2017)... ... January 20, 2017 , ... ... sugar-free alternative VW+ 002. The drinks have been produced in collaboration with Zlatan ... perform during your workout. , After a successful launch in Sweden last year, ...
(Date:1/20/2017)... ... , ... “I Forgive You”: a fine examination of how God handles sin, including how ... published author, Stephen Miller, who, for over ten long years has been waiting to release ... Trinidad and Tobago, he has been serving the Lord for over twenty years, and he ...
(Date:1/20/2017)... ... ... “Knowledge is God’s Lighthouse”: a moving and colorful collection of prayers that reminds ... published author, Gene Gaapf, a retired truck driver, and a long-time writer, whose published ... high school and have many different titles,” Gaapf mentions about his different works. “I ...
Breaking Medicine News(10 mins):
(Date:1/19/2017)... 19, 2017  Abaxis, Inc. (NasdaqGS: ABAX ... instruments and consumables for the medical and veterinary markets ... financial results for the third quarter fiscal year 2017, ... 4:15 p.m. ET on Thursday, January 26, 2017.  The ... fiscal year 2017 after the market closes on Thursday, ...
(Date:1/19/2017)...   Science Exchange , the leading marketplace ... the first five replication studies from the ... in eLife today. Despite intense scrutiny around reproducibility ... evaluation of reproducibility rates that may identify specific ... assessments of reproducibility, the results of this project ...
(Date:1/19/2017)... , January 18, 2017 , , Marks E-QURE ... distribution agreement, following similar agreements in ... Wound care is $2 5 ... E-QURE Corp. (OTCQB: EQUR), a leader in medical devices for the treatment ... - Médica Equipos Médicos S.A.S. (TeckMedica) in Colombia for ...
Breaking Medicine Technology: