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Cellular prion protein transduces neuroprotective signals
Luciana B Chiarini1, Adriana R O Freitas, Silvio M Zanata
1Instituto de Biofísica da UFRJ, CCS, bloco G, Cidade Universitária, 21949-900, Rio de Janeiro, Brasil.
The EMBO Journal
|July 3, 2002
Summary
The cellular prion protein (PrP(c)) plays a neuroprotective role. Activating PrP(c) with a specific peptide triggers a cAMP/protein kinase A (PKA) pathway, preventing cell death in retinal cells.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- The cellular prion protein (PrP(c)) is implicated in various cellular functions.
- Its role in cell death and survival pathways remains incompletely understood.
Purpose of the Study:
- To investigate the involvement of PrP(c) in neuronal cell death.
- To elucidate the signaling pathways activated by PrP(c) engagement.
Main Methods:
- Utilized retinal explants from wild-type and PrP(c)-null mice.
- Induced apoptosis using anisomycin (ANI).
- Administered a PrP(c)-binding peptide and various inhibitors (phosphatidylinositol-specific phospholipase C, PKA inhibitor, MEK/Erk inhibitor) and antibodies.
Main Results:
- A PrP(c)-binding peptide partially prevented ANI-induced cell death in wild-type, but not PrP(c)-null, retinal explants.
- This neuroprotection was dependent on cAMP/protein kinase A (PKA) activation and abolished by PKA inhibition or phosphatidylinositol-specific phospholipase C treatment.
- Antibodies to PrP(c) that increased cAMP also conferred neuroprotection, while MEK/Erk inhibition had no effect.
Conclusions:
- PrP(c) engagement initiates neuroprotective signals via a cAMP/PKA-dependent pathway.
- PrP(c) may function as a trophic receptor, promoting a neuroprotective state upon activation.