Selective PDE4 subtype inhibition provides new opportunities to intervene in neuroinflammatory versus myelin damaging hallmarks of multiple sclerosis

•Selective inhibition of PDE4 gene products and isoforms provides new opportunities in the PDE4 inhibition field, especially for MS.•Selective PDE4B inhibition suppresses inflammatory responses by phagocytes.•PDE4D, but not PDE4B inhibition promotes oligodendrocyte differentiation and thus enhances remyelination.•The therapeutic dose of the applied PDE4B and PDE4D inhibitors does not induce emetic side effects.•PDE4D isoform fingerprints in human area postrema neurons and MS lesions reveal novel targets to stimulate remyelination while avoiding emesis.