Several signaling pathways are involved in a wide range of physiological functions, with increasingly awareness that intercellular and intracellular signal transduction aberrations may underlie the pathogenesis of many diseases. Consequently, attempts to target such signaling abnormalities have become a common theme in the design of new therapeutic strategies. In particular, two antagonistic signaling pathways, mediated by cyclic adenosine 3',5' monophosphate (cAMP) and nitric oxide (NO) play a role in a variety of disease states including Alzheimer’s disease, polycystic kidney disease, prostate cancer, atopic dermatitis, osteoarthritis, septic shock, congestive heart failure and rheumatoid arthritis. As such, methods to counteract and reverse disease-causing signaling defects may be advantageous for various conditions.
Researchers at the University of Michigan have developed a method to treat a disease with an underlying signal transduction aberration via administration of shared epitope (SE)- or SE motif-containing peptide, which may be conjugated to a carrier molecule. In particular, such peptide has been shown to selectively activate NO-cGMP-PKG pathway with reciprocal effect on cAMP-PKA pathway. As cAMP-PKA signaling and/ or inadequate NO-cGMP response are implicated in variety of pathogeneisis, this approach may be explored for many applications, via targeted delivery. In addition, the SE motif presented here in provide neuroprotective effects of ApoE, APLP1, and laminin, and may account for the negative association between Alzheimer’s disease and rheumatoid arthritis.
Applications and Advantages
- Treatment for disease involving aberrant NO-cGMP-PKG/ cAMP-PKA pathways including Alzheimer’s disease and rheumatoid arthritis.
- May be applicable to a variety of disease states, with targeted delivery.