Featured Research

from universities, journals, and other organizations

New insight into dementia pathophysiology

Date:
November 17, 2010
Source:
Cell Press
Summary:
New research unravels a key molecular pathway underlying a neurodegenerative disorder that causes a devastating type of dementia. The study sheds light on the pathological processing of Progranulin, a protein that normally promotes the survival of brain cells but is reduced in some neurodegenerative diseases.

Frontotemporal lobar degeneration (FTLD) refers to a group of disorders associated with degeneration of the frontal and temporal lobes of the brain. Symptoms include dementia, aphasia, and semantic disorders. Mutation of the gene for PGRN is associated with the most common form of FTLD, which is also characterized by inclusions of TDP-43 protein in the brain. Abnormal accumulation of TDP-43 has also been linked with amyotrophic lateral sclerosis (ALS).

While it is clear that a reduction in PGRN is causative for FTLD-TDP, the underlying mechanism is unknown. "Elucidation of PGRN action and the control of PGRN levels may have broad relevance for both FTLD and ALS," explains senior study author, Dr. Stephen M. Strittmatter from Yale University School of Medicine. "In order to advance the understanding of PGRN biology, we searched for cell surface binding sites that interact with PGRN."

Dr. Strittmatter and colleagues identified Sortilin as a key PGRN binding site on the surface of cortical neurons. In the stressed nervous system, PGRN was not expressed in neurons, but in nearby glial cells. Sortilin rapidly transferred PGRN inside of the neurons and delivered it to lysosomes, cellular structures that degrade proteins. Mice that did not express Sortilin exhibited high levels of extracellular PGRN. Importantly, mice with a PGRN deficiency similar to that seen in FLTD-TDP, were fully normalized with regards to PGRN levels when Sortilin was deleted.

Taken together, the findings implicate Sortilin-mediated PGRN endocytosis in FTLD-TDP pathophysiology and identify Sortilin binding as a potential therapeutic site to alter PGRN pathology. However, the authors are careful to caution that additional studies elucidating the connection between PGRN, Sortilin, and TDP-43 are needed. "Future functional studies of Sortilin in PGRN biology will require development of robust rodent models for PGRN-dependent neurodegeneration," says Dr. Strittmatter. "Nevertheless, our work implicates Sortilin-mediated PGRN endocytosis as a key pathway for further study in FTLD, and possible ALS, pathophysiology."


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "New insight into dementia pathophysiology." ScienceDaily. ScienceDaily, 17 November 2010. <www.sciencedaily.com/releases/2010/11/101117121801.htm>.
Cell Press. (2010, November 17). New insight into dementia pathophysiology. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2010/11/101117121801.htm
Cell Press. "New insight into dementia pathophysiology." ScienceDaily. www.sciencedaily.com/releases/2010/11/101117121801.htm (accessed October 1, 2014).

Share This



More Health & Medicine News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Some Positive Ebola News: Outbreak 'Contained' In Nigeria

Some Positive Ebola News: Outbreak 'Contained' In Nigeria

Newsy (Sep. 30, 2014) The CDC says a new case of Ebola has not been reported in Nigeria for more than 21 days, leading to hopes the outbreak might be nearing its end. Video provided by Newsy
Powered by NewsLook.com
UN Ebola Mission Head: Immediate Action Is Crucial

UN Ebola Mission Head: Immediate Action Is Crucial

AFP (Sep. 30, 2014) The newly appointed head of the United Nations Mission for Ebola Emergency Response (UNMEER), Anthony Banbury, outlines operations to tackle the virus. Duration: 00:39 Video provided by AFP
Powered by NewsLook.com
CDC Confirms First Case of Ebola in US

CDC Confirms First Case of Ebola in US

AP (Sep. 30, 2014) The CDC has confirmed the first diagnosed case of Ebola in the United States. The patient is being treated at a Dallas hospital after traveling earlier this month from Liberia. (Sept. 30) Video provided by AP
Powered by NewsLook.com
New Breast Cancer Drug Extends Lives In Clinical Trial

New Breast Cancer Drug Extends Lives In Clinical Trial

Newsy (Sep. 30, 2014) In a clinical trial, breast cancer patients lived an average of 15 months longer when they received new drug Perjeta along with Herceptin. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins