| First Author | La Vitola P | Year | 2019 |
| Journal | Brain | Volume | 142 |
| Issue | 2 | Pages | 249-254 |
| PubMed ID | 30601948 | Mgi Jnum | J:360672 |
| Mgi Id | MGI:7782661 | Doi | 10.1093/brain/awy318 |
| Citation | La Vitola P, et al. (2019) Cellular prion protein neither binds to alpha-synuclein oligomers nor mediates their detrimental effects. Brain 142(2):249-254 |
| abstractText | alpha-Synuclein oligomers are crucial players in the pathogenesis of Parkinson's disease. Some mechanisms involved in alpha-synuclein oligomer detrimental effects include membrane damage, neuroinflammation and protein-protein interactions. Recently, the cellular prion protein (PrPC) emerged as an interactor of alpha-synuclein oligomers, apparently mediating their detrimental activities. Through direct in vivo and in vitro approaches we herein investigated the existence of a direct cross-talk between alpha-synuclein oligomers and PrPC. In vitro, we assessed alpha-synuclein oligomer toxicity by comparing the effect in Prnp+/+ versus PrPC knockout (Prnp0/0) hippocampal neurons. Through an in vivo acute mouse model, where alpha-synuclein oligomers injected intracerebroventricularly induce memory impairment and neuroinflammation, we verified whether these detrimental effects were preserved in Prnp0/0 mice. In addition, PrPC-alpha-synuclein oligomer direct binding was investigated through surface plasmon resonance. We found that PrPC was not mandatory to mediate alpha-synuclein oligomer detrimental effects in vitro or in vivo. Indeed, alpha-synuclein oligomer toxicity was comparable in Prnp+/+ and Prnp0/0 neurons and both Prnp+/+ and Prnp0/0 mice injected with alpha-synuclein oligomers displayed memory deficit and hippocampal gliosis. Moreover, surface plasmon resonance analyses ruled out PrPC-alpha-synuclein oligomer binding. Our findings indicate that PrPC neither binds alpha-synuclein oligomers nor mediates their detrimental actions. Therefore, it is likely that PrPC-dependent and PrPC-independent pathways co-exist in Parkinson's disease. |
