PrP(C) signalling in neurons: from basics to clinical challenges

Area of Science:

• Neuroscience
• Molecular Biology
• Prion Biology

Background:

• The cellular prion protein (PrP(C)) is the normal form of the protein implicated in Transmissible Spongiform Encephalopathies (TSEs).
• PrP(C) is abundant in neurons and essential for prion-induced neurotoxicity.
• PrP(C) functions as a cell signaling molecule involved in neuronal survival and plasticity.

Purpose of the Study:

• To review signal transduction cascades mediated by neuronal PrP(C).
• To summarize how PrP(C) signaling is subverted in TSEs and Alzheimer's disease (AD).
• To discuss the clinical implications of PrP(C) signaling dysregulation.

Main Methods:

• Literature review and synthesis of existing research on PrP(C) signaling.
• Analysis of studies investigating PrP(C) interactions with pathogenic agents like PrP(Sc) and amyloid-beta (Aβ) oligomers.
• Discussion of evidence linking PrP(C) signaling to neuropathogenesis.

Main Results:

• PrP(C) mediates various signal transduction pathways in neurons.
• Prion protein (PrP(Sc)) and Aβ oligomers corrupt PrP(C) signaling to cause neurotoxicity.
• Dysregulated PrP(C) signaling contributes to the pathology of TSEs and AD.

Conclusions:

• PrP(C) is a key player in neuronal signaling, with its normal function being critical for brain health.
• Targeting PrP(C) signaling pathways may offer therapeutic strategies for prion diseases and AD.
• Understanding PrP(C) signaling provides insights into shared mechanisms of neurodegenerative diseases.