Abstract: T h e u m b re l l a t e r m “ n e u ro d e g e n e ra t i v e disorders” (NDDs) refers to several conditions characterized by a progressive loss of structure and function of cells belonging to the nervous system. Such diseases affect more than 50 million people worldwide. Neurodegenerative disorders are characterized by sundry factors and pathophysiological mechanisms that are challenging to be fully profiled. Many of these rely on cell signaling pathways to preserve homeostasis, involving second messengers such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine 3′,5′-monophosphate (cGMP). Their ability to control the duration and amplitude of the signaling cascade is given by the presence of several common and uncommon effectors. Protein kinases A and G (PKA and PKG), phosphodiesterases (PDEs), and scaffold proteins are among them.