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GENETICS
GENETICS
Psoriasis is linked to a gene mapped to the distal end of the 17th chromosome (see article from Dermatology Times, "Spice Shows Promise as Powerful Skin Disease Treatment"). This gene encodes an abnormal cyclic AMP (Type II) which fails to switch-off the activity of phosphorylase kinase. After injury (trauma, allergic reactions, infections), phosphorylase kinase activity is induced.
Elevated phosphorylase kinase activity not only breaks down glycogen into ATP needed for multiple reactions, but activates IkBa kinase, a key enzyme responsible for activating NFkB, a transcription activator. Activation of NFkB then goes on to turn on over 200 genes responsible for cell proliferation, cell cycling, inhibition of apoptosis etc, resulting in the formation of PCNA+ (proliferating cell nuclear antigen), detected by the immunocytochemical marker, Ki-67+ . The Ki-67+ cells are capable of producing new cells and their increased numbers in the basal keratinocyte layers of the psoriatic epidermis is responsible for the hyper-proliferation characteristic of the psoriatic disease.
Phosphorylase kinase is activated by "injury stimuli", which releases Type I cAMP protein kinase, which further activates the phosphorylase kinase molecule by a conformational change in the molecule, which allows access to phosphorylation sites for reactivity. After the "wound" is healed, the activation of Type II cAMP protein kinase “closes up” the molecule, thus switching off phosphorylase kinase activity by obscuring these phosphorylation sites.
The abnormal Type II protein kinase in psoriatic individuals results in an inability to switch off phosphorylase kinase activity. The psoriatic skin is, therefore, chronically in the proliferating mode.