Pathological Role of Peptidyl-Prolyl Isomerase Pin1 in the Disruption of Synaptic Plasticity in Alzheimer’s Disease

Figure 6

Blocking of Pin1 activity blocks NMDA receptor-mediated turnover of Skank3 and increases degradation of Shank3 and PSD95 induced by oligomers of Aβ and NMDA in cultured neurons. Cortical neurons at 15 DIV were incubated with memantine, NMDA, PiB, and oligomers of Aβ for 24 h. (a) Representative Western blot. (b and c) Results from densitometric imaging of these tests. Memantine 10 μM significantly decreased levels of Shank3 and PSD95 proteins. NMDA 100 nM significantly increased levels of these proteins, and 10 μM memantine significantly inhibited the increase of Shank3 induced by 100 nM NMDA. When 10 μM NMDA and 0.5 μM PiB were incubated with neuron together, these proteins were significantly decreased. The same results were observed between PiB and oligomers of Aβ from seven independent experiments ( dishes for each experimental condition, , ).

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