Fig. 6

Proposed model for the role of microglial and neuronal amylin receptors in mediating the amyloid beta (Aβ)-induced neurodegeneration. Amylin receptors, comprised of calcitonin receptor (CTR) and receptor activity modifying protein 3 (RAMP3), are expressed on both neurons and the microglia. The expression of amylin receptors on microglial cells is increased in response to inflammatory triggers, such as lipopolysaccharide (LPS), resulting in activation of these cells. Interaction of Aβ with amylin receptors on the activated microglia leads to increased production and release of cytokines, which act directly on neurons to produce cell death and additionally augment the production of Aβ via processing of the amyloid precursor protein (APP). This Aβ, in turn, interacts with neuronal and microglial amylin receptors to produce cell death. The amylin receptor antagonist AC253 acts on both the neuronal and microglial receptors to block the detrimental effects of Aβ and affords protection against the neuronal degeneration