Altered Neuron Excitability and Synaptic Plasticity in the Cerebellar Granular Layer of Juvenile Prion Protein Knock-Out Mice with Impaired Motor Control

Cellular Form of Prion Protein Inhibits Reelin-Mediated Shedding of Caspr from the Neuronal Cell Surface to Potentiate Caspr-Mediated Inhibition of Neurite Outgrowth

“…In the context of our study it is noteworthy that differentiation of granule cells and cerebellar network formation is retarded in PrP-deficient mice, confirming the role of PrP in brain development (Prestori et al, 2008). In our present study, the potentiating effect of PrP on inhibition of neurite outgrowth was tested not only in vitro but also in vivo; in agreement with our in vitro data, constitutive absence of PrP in mice leads to enhanced regeneration after spinal cord injury in terms of recovery of locomotor functions and regrowth of serotonergic and adrenergic axons into the caudal part of the lesioned spinal cord of adult mice.…”

Prion and TNFα: TAC(E)it agreement between the prion protein and cell signaling

“…Also in agreement with our results is the demonstration that the absence of PrP C protracted both mitosis of cerebellar granule cell precursors and maturation of the granule layer in the first post-natal weeks, and that both events did not compromise the final acquisition of a normal architecture of the cerebellum. 25 Thus, all these findings support the contention that, by affecting the rate, but not the end point, of tissue morphogenesis, PrP C is involved in the maturation of different tissues. As our data have highlighted the importance of using in vivo models to best decipher the physiologic action of PrP C , this same mean of experimentation could be used to…”

Is indeed the prion protein a Harlequin servant of "many" masters?

“…The latter notion is consistent with the delayed maturation of different types of PrP C -less neurons, observed both in vitro and in vivo. 32,33 If one assumes that the interaction of PrP C with multiple partners (45 for PrP C and PrP Sc , as reviewed in Aguzzi et al, 5 or 46 considering the homophylic interaction) are all functionally significant, the most immediate interpretation of this "sticky" behavior entails that PrP C acts as a scaffolding protein in different membrane protein complexes. 5,6 Each complex could then activate a specific signaling pathway depending on the type and maturation of cells, the expression and glycosylation of PrP C , and availability of extra-and intra-cellular signaling partners.…”