Navigation Links
New insight into dementia pathophysiology
Date:11/17/2010

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."


'/>"/>

Contact: Elisabeth (Lisa) Lyons
elyons@cell.com
617-386-2121
Cell Press
Source:Eurekalert

Related biology technology :

1. Protein Research Marketing Insights
2. BioTrends Releases TreatmentTrends(TM): Nephrology and Renal Dietitians, Two Syndicated Reports Providing Continuing Insight into the Management of Renal Anemia, Hyperphosphatemia, and Secondary Hyperparathyroidism
3. Posit Science(R) Corporation Announces the Release of InSight(TM) 1.1
4. European Nephrologists Share Insights on the Management of Renal Anemia and Hyperphosphatemia in Latest BioTrends Report
5. BioTrends Releases TreatmentTrends(TM): US Nephrology, an Ongoing Syndicated Publication Providing Insight into Physician Perceptions and Management of Renal Anemia, Hyperphosphatemia, and Secondary Hyperparathyroidism
6. Jatropha Sector Reality Check: Still Viable In Volatile Times? Upcoming Webcast Shares Latest Insights
7. Museomics yields new insights into extinct Tasmanian tiger
8. New Study Shares Insights for Competitive Intelligence Policies, Ethics and Data Collection
9. ExL Pharma Presents The Pharmaceutical Managed Markets Insight & Marketing for the Pharmaceutical Industry Conference
10. Stephen H. Friend, MD, PhD to Keynote at Defined Healths 9th Annual Therapeutic Insight Conference
11. PAREXEL Experts to Present Leading Insights at Drug Information Association 21st Annual Euromeeting
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/14/2017)... NY (PRWEB) , ... August 14, 2017 , ... ... Clinical Trials event, which will take place on September 6, 2017 at the ... Karlin, MD , Head of Experimental Medicine, Informatics, and Regulatory Strategy, Pfizer Innovative Research ...
(Date:8/11/2017)... ... August 11, 2017 , ... Algenist continues to disrupt ... unlocking collagen like never before. , Collagen is the key structural element skin ... with Liquid Collagen™, which include: , First to market ...
(Date:8/10/2017)... ... August 09, 2017 , ... ... week-- as students. From August 14th through the 16th, the University City Science ... in the summer of 2016, provides Philadelphia-based middle school educators an opportunity for ...
(Date:8/10/2017)... Grand Bahama (PRWEB) , ... August 09, 2017 , ... ... will take place at the Pelican Bay Hotel in Freeport, Grand Bahama on ... and pre-registration is required. , With oversight from the Ministry of Health’s National ...
Breaking Biology Technology:
(Date:4/11/2017)... 11, 2017 No two people are ... the New York University Tandon School of Engineering ... found that partial similarities between prints are common ... mobile phones and other electronic devices can be ... vulnerability lies in the fact that fingerprint-based authentication ...
(Date:4/5/2017)... , April 5, 2017 Today ... announcing that the server component of the HYPR platform ... for providing the end-to-end security architecture that empowers biometric ... HYPR has already secured over 15 million users ... including manufacturers of connected home product suites and physical ...
(Date:3/30/2017)... LOS ANGELES , March 30, 2017  On ... Hack the Genome hackathon at ... This exciting two-day competition will focus on developing health ... experience. Hack the Genome is ... has been tremendous. The world,s largest companies in the ...
Breaking Biology News(10 mins):