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:2/23/2017)... ... February 23, 2017 , ... ... 12th annual Inventors Recognition Reception at Purdue Research Park of West ... member in recognition of outstanding contributions to, and success with, commercializing discoveries from ...
(Date:2/23/2017)... 2017 Aviva Systems Biology Corporation (ASB) ... of GenWay Biotech Incorporated, a protein solutions and ... offering for both the research and diagnostic markets. ... enhance capabilities for both entities. GenWay,s 18 years of ... nicely complement ASB,s objective to become a leading ...
(Date:2/22/2017)... ... February 22, 2017 , ... Kernel ... Kendall Research Systems, LLC (KRS) clinical development program. KRS is a neurotechnology ... for research and clinical applications. The terms of the transaction were not disclosed. ...
(Date:2/22/2017)... ... February 22, 2017 , ... ... provider of women’s health, primary care, and specialty education, announced today it ... Education (ACCME). ACCME’s Accreditation with Commendation is a six-year accreditation and is ...
Breaking Biology Technology:
(Date:1/26/2017)... CITY , Jan. 26, 2017  Crossmatch, a ... unveiled a new solution aimed at combatting fraud, waste ... solution was introduced at the Action on Disaster Relief ... key meeting point for UN agencies and foreign assistance ... Fraud, waste and abuse are a largely unacknowledged ...
(Date:1/24/2017)... , Jan. 24, 2017  It sounds ... baby,s sock that monitors vital signs and alerts ... an infant,s oxygen saturation level drops. But pediatric ... alarm to parents, with no evidence of medical ... devices are marketed aggressively to parents of healthy ...
(Date:1/19/2017)... 19, 2017 Sensory Inc ., ... security for consumer electronics, and i ... and cybersecurity solutions, today announced a global partnership ... institutions worldwide to bolster security of data sensitive ... user authentication platforms they offer, innerCore now offers ...
Breaking Biology News(10 mins):