Role of Progranulin in Neurodegenerative Disease

Reference #:

2006-130

Inventors/Contributors

Michael L. Hutton Ph.D., Matthew C. Baker, Jennifer M. Gass, Rosa Rademakers, Ph.D., Jason Eriksen, Ph.D.

Description

Frontotemporal dementia (FTD) is the second most common cause of dementia in people under 65 years. A large proportion of FTD patients (35-50%) have a family history of dementia consistent with a strong genetic component to the disease. In these families, tau-negative FTD is caused by truncating mutations in the gene encoding Progranulin (PGRN) which is located on chromosome 17q21. PGRN is a 68.5 kDa secreted growth factor, involved in the regulation of multiple processes including wound repair, development and inflammation; PGRN has also been strongly linked to tumorigenesis. PGRN expression is increased in activated microglia in multiple neurodegenerative diseases including Creutzfeldt-Jakob disease (CJD), Motor Neuron Disease (MND), and Alzheimer’s Disease (AD). We have identified mutations in PGRN as the cause of neurodegenerative disease and indicate the importance of PGRN function for neuronal survival. This may suggest that loss of growth factor support is a common mechanism of neurodgeneration in these human diseases.

Patent Status

Pending