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Review
. 2018 Feb 28;38(9):2146-2148.
doi: 10.1523/JNEUROSCI.3307-17.2018.

A Role for Cellular Prion Protein in Late-Onset Alzheimer's Disease: Evidence from Preclinical Studies

Ricardo A S Lima-Filho  1 , Mauricio M Oliveira  2
Affiliations
Review

A Role for Cellular Prion Protein in Late-Onset Alzheimer's Disease: Evidence from Preclinical Studies

Ricardo A S Lima-Filho et al. J Neurosci. .
No abstract available

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Figures

Figure 1.
Figure 1.
AβO-induced PrPC signaling and neuroinflammation converge to cause cognitive decline. AβOs can bind to and trigger abnormal signaling cascade in both neurons and glial cells. At synapses, AβOs bind to PrPC and recruit mGluR5, forming a multiprotein complex. This complex signals to increase activation of Fyn and inactivation of eEF2, resulting in reduced protein synthesis. Depletion of PrPC, pharmacological modulation of mGluR5 by using Silent Allosteric Modulation (SAM) or inhibition of Fyn restores cognition. AβOs also induce neuroinflammation, which also leads to cognitive decline. Anti-inflammatory agents, on the other hand, can rescue cognition. Thus, neuroinflammation and PrPC may be convergent or parallel pathways leading to cognitive decline in AD. Neurons and glial cells were adapted from the software Mind The Graph. Left Inset, Expanded view of the synapse, showing AβO-PrPC-mGluR5 activity leading to Fyn activation and eEF2 inactivation. Right Inset, Reprinted with permission (Ledo et al., 2016). Hippocampal slice treated with AβOs and immunostained for Iba-1 and DAPI, showing pronounced microgliosis.
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