Model of the interactions between mGluR5, PrP^C, and anti-PrP antibodies.

<p>(<b>A</b>) In untreated neurons, mGluR5-PrP^C complexes are distributed within and outside spines. Upon exposure to prion-mimetic antibodies (<b>B</b>), mGluR5 translocates to the spine, where it may enhance neurotoxicity by contributing to a Ca²⁺ overload. (<b>C</b>) Exposure to POM2, in contrast, engages the N-terminal “flexible tail” of PrP^C, thereby making it unavailable to mGluR5. Consequently, mGluR5-PrP^C (and possibly also mGluR1-PrP^C) complexes do not translocate to spines. As a result, POM2 affords functional neuroprotection similarly to mGluR5 antagonists. (<b>D</b>) We speculate that prion infection may trigger topological rearrangements similar to those observed after POM1 exposure.