PrP meets alpha-synuclein: Molecular mechanisms and implications for disease

Area of Science:

• Neuroscience
• Molecular Biology
• Protein Chemistry

Background:

• Prion protein (PrP) discovery revolutionized understanding of protein-misfolding diseases.
• Alpha-synuclein (aSyn) misfolding and aggregation drive Parkinson's disease and synucleinopathies.
• Cell-to-cell spread of aSyn pathology is a key disease mechanism.

Purpose of the Study:

• To provide a comprehensive overview of the interaction between aSyn and cellular PrP (PrP^C).
• To discuss the role of this interaction in synucleinopathies.
• To identify knowledge gaps and potential therapeutic avenues.

Main Methods:

• Review of existing literature on PrP and aSyn structure, function, and aggregation.
• Analysis of studies investigating PrP^C as a receptor for protein aggregates.
• Synthesis of current understanding of aSyn-PrP^C interactions.

Main Results:

• PrP^C may function as a receptor or sensor for aSyn aggregates.
• This interaction is implicated in the cell-to-cell transmission of aSyn pathology.
• PrP^C's role is observed across various neurodegenerative disorders.

Conclusions:

• The interaction between aSyn and PrP^C is a critical factor in synucleinopathy progression.
• Understanding this interplay may reveal novel therapeutic strategies for Parkinson's disease and related disorders.
• Further research is needed to fully elucidate the mechanisms and therapeutic potential.