Alterations in cyclic nucleotide signaling are implicated in healthy aging and age-related pathologies of the brain

It is not only important to consider how hormones may change with age, but also how downstream signaling pathways that couple to hormone receptors may change. Among these hormone-coupled signaling pathways are the 3',5'-cyclic guanosine monophosphate (cGMP) and 3',5'-cyclic adenosine monophosphate (cAMP) intracellular second messenger cascades. Here, we test the hypothesis that dysfunction of cAMP and/or cGMP synthesis, execution, and/or degradation occurs in the brain during healthy and pathological diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Although most studies report lower cyclic nucleotide signaling in the aged brain, with further reductions noted in the context of age-related diseases, there are select examples where cAMP signaling may be elevated in select tissues. Thus, therapeutics would need to target cAMP/cGMP in a tissue-specific manner if efficacy for select symptoms is to be achieved without worsening others.