Text Size Normal Text Sizing Button Medium Text Sizing Button Large Text Sizing Button Text Contrast Normal Contrast Button Reverse Contrast Button Switch to Spanish Language Contact Us Sitemap Sign In Register
Link to Homepage About AHAF
Donate Now Get Involved  
Alzheimer's Disease Research Macular Degeneration Research National Glaucoma Research


Sign up for Email Notifications
If you would like to be notified when submission deadlines are announced please click on the link below.

Sign up for new RFP announcements and submission deadline notifications.

This email list is not sold or distributed, and serves only as an annual reminder of the availability of research funding through the American Health Assistance Foundation (www.ahaf.org). Please follow instructions on the notification emails for removal requests.
 

Researchers:
Have you heard a story, statistic, or discovery that might interest the public? Let us know about it!
 
AHAF Research Grants Funding
Grant Funding for Alzheimer's Research
Grant Funding for Macular Degeneration Research
Grant Funding for Glaucoma Research
 

  

Alzheimer's Disease Research - Current Award

Photo Pending

Chunyu Wang, M.D., Ph.D.

Rensselaer Polytechnic Institute
Troy, NY

Title: Structural Basis Of FAD Mutations Within The Transmembrane Domain Of APP
Non-Technical Title: Structural Biology Of Amyloid Beta Generation

Duration: April 1, 2009 - March 31, 2011
Award Type: Pilot
Award Amount: $150,000


Summary:

This project aims to define the structural characteristics of trans-membrane portion of Amyloid Precursor Protein (APPTM ) as a gamma-secretase substrate that plays a role in determining the amyloid beta 42/amyloid beta 40 ratio. This will be achieved by combining a gamma-secretase assay and structural determination of normal and a variety of mutant forms of APPTM.

Details:


Understanding the generation of amyloid beta by a key enzyme, gamma-secretase is critical for developing disease-modifying treatment of Alzheimer's disease. Although intense efforts are devoted to the structural biology of gamma-secretase, little attention is paid to the substrate of gamma-secretase, the transmembrane domain of the amyloid precursor protein (APPTM ). This project will study the 3D structures of APPTM and their relevance to the generation of the more toxic form of amyloid beta. Understanding the structural determinants of the substrate will generate great insight to the development of Alzheimer's disease and for designing gamma-secretase inhibitors and modulators.

We will 1) solve the structure of APPTM and 2) correlate structural characteristics of APPTM with properties in amyloid beta production.

Progress Updates:

Mutations within the transmembrane domain of APP (APPTM) protein are known to cause Alzheimer's disease, but their pathologic mechanism is not understood. The transmembrane domain of a protein is normally buried in the fatty, protective envelope, or membrane, of a cell. We have generated crucial protein samples for detailed comparison of the 3D structures of APPTM wild-type and disease-causing protein mutants, using solution nuclear magnetic resonance (NMR) methods. NMR methods determine the structure of proteins (and other chemicals) by taking measurements of the natural magnetic properties of the atoms that make up a protein. Data are being collected which will lead to atomic resolution structures of the APPTM protein. This information may give novel insights into the pathogenesis of Alzheimer’s disease, leading to new treatment possibilities.