Asset Details
Do you wish to reserve the book?
The Role of Prion Protein in Reelin/Dab1 Signaling: Implications for Neurodegeneration
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
The Role of Prion Protein in Reelin/Dab1 Signaling: Implications for Neurodegeneration
Do you wish to request the book?
The Role of Prion Protein in Reelin/Dab1 Signaling: Implications for Neurodegeneration
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
The Role of Prion Protein in Reelin/Dab1 Signaling: Implications for Neurodegeneration
2025
Overview
The cellular prion protein (PrPC) is studied in prion diseases, where its misfolded isoform (PrPSc) leads to neurodegeneration. PrPC has also been implicated in several physiological functions. The protein is abundant in the nervous system, and it is critical for cell signaling in cellular communication, where it acts as a scaffold for various signaling molecules. The Reelin signaling pathway, implicated both in Alzheimer’s and prion diseases, engages Dab1, an adaptor protein influencing APP processing and amyloid beta deposition. Here, we show, using Prnp knockout models (Prnp0/0), that PrPC modulates Reelin signaling, affecting Dab1 activation and downstream phosphorylation in both neuronal cultures and mouse brains. Notably, Prnp0/0 mice showed reduced responsiveness to Reelin, associated with altered Dab1 phosphorylation and Fyn kinase activity. Even though no direct interaction between PrPC and Reelin/ApoER2 was found, Prnp0/0 neurons showed lower NCAM levels, a well-established PrPC interactor. Prion infection further disrupted the Reelin signaling pathway, thus downregulating Dab1 and Reelin receptors and altering Reelin processing, like Alzheimer’s disease pathology. These findings emphasize PrPC indirect role in Dab1 signaling via the NCAM and Fyn pathways, which influence synaptic function and neurodegeneration in prion diseases.
Publisher
MDPI AG,MDPI
Subject
/ Adaptor Proteins, Signal Transducing - metabolism
/ Animals
/ Brain
/ Cell Adhesion Molecules, Neuronal - genetics
/ Cell Adhesion Molecules, Neuronal - metabolism
/ Cellular signal transduction
/ cleavage
/ Dab1
/ Embryos
/ Extracellular Matrix Proteins - genetics
/ Extracellular Matrix Proteins - metabolism
/ Humans
/ Kinases
/ LDL-Receptor Related Proteins
/ Mice
/ Nerve Tissue Proteins - genetics
/ Nerve Tissue Proteins - metabolism
/ Neural cell adhesion molecule
/ Neurons
/ Prions
/ Proteins
/ Proto-Oncogene Proteins c-fyn - metabolism
/ Reelin
/ Serine Endopeptidases - genetics
