Friday, January 11, 2013

RNA Targets Therapeutic for the Alzheimer's Disease Amyloid Precursor Protein

 Our goal to suppress Alzheimer's APP gene expression at the translational level has the advantage that the APP 5'UTR RNA target is unique, thus affording a higher degree of selectivity.

    There are regulatory sites in the 3'UTR of APP mRNA that can be utilized as targets to suppress APP gene expression. However, our finding that the 5'UTR of APP mRNA is a powerful, translational enhancer element makes this RNA structure a very attractive target for regulating APP gene expression as a therapeutic strategy to slow AD progression.

      The vaccination strategy to target and suppress steady-state levels of A(3 peptide has been successfully developed by Elan Pharmaceuticals, who reduced later stage formation of (3-amyloid plaques, neuritic dystrophy, and astrogliosis, and other "Alzheimer's disease-like pathology" in the PDAPP transgenic mouse. RNA targeting and vaccination approaches may ultimately be complementary approaches as therapeutic strategies to help AD patients.

   Werstuck and Green  demonstrated a model system for the selection of RNA-binding compounds to inhibit translation of reporter proteins under the control of specific upstream RNA stemloops.

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