Summary: A lipid anchor on nerve cell membranes stabilizes prion proteins ( PrPC ) and stops their pathological aggregation into forms linked to prion diseases. Researchers created fresh in vivo and cell models to investigate how membrane anchoring blocks these dangerous transformations.
Pre-formed particles can also cause clumping, which is consistent with what they discovered about infectious prion diseases. These findings may help doctors develop treatment options for prion and another neurodegenerative diseases by providing important insights into peptide misfolding.
Important Information:
- Lipid Anchors Role: Membrane cables stabilize prion enzymes, preventing compulsive formation.
- Disease Mechanism: Pre-formed particles may cause blending of tethered prion protein, related to viral prion diseases.
- Medical Perspective: Recognizing protein restoration might be helpful in developing treatments for prion and associated conditions.
Origin: RUB
Protein formation is typical of several neurological diseases such as Alzheimer’s, Parkinson’s and prion conditions such as Creutzfeld-Jakob condition.
A study team led by Professor Jörg Tatzelt from the German Ruhr University Bochum has now demonstrated that a fat outlet on the outer layer of brain cells blocks the prion protein’s formation using novel in vitro and cell culture models.
Understanding the procedures that lead the formerly folded proteins to change into infectious forms is of vital importance for the creation of medical strategies, says Jörg Tatzelt.
The team published their findings in the journal , Proceedings of the National Academy of Sciences ( PNAS ) on December, 31, 2024.
Both the disease’s congenital and infected forms are present.
Prion illnesses are dangerous aging brain diseases. They are linked to the transformation of the healthy fold of the cellular prion protein ( PrPC ) into pathological aggregates, i .e., scrapie prion protein ( PrPSc ). Inheritance prion diseases are triggered by genetic variants, albeit these are uncommon in individuals.
Some gene variants affect the framing of PrPC , to the body layer. But, how precisely these changes may cause prion diseases is still unexplored.
The researchers have created new types to investigate the role of a barrier anchor in the fold and formation of PrP in both in vitro and in cerebral cells in order to gain new perspectives into the underlying processes.
The research demonstrated that adhering to membranes successfully stops formation and stabilizes the folding of PrP.
” What’s fascinating is that the blending of membrane-anchored PrP may be induced by pre-formed protein aggregate”, says Jörg Tatzelt.
This is a process that might be involved in the spread of prion illnesses.
Funding: The study was funded by the German Research Foundation: TA 167/6-3, WI/2111-6 and Cluster of Excellence Ruhr Explores Solvation ( RESOLV, EXC 2033–390677874 ).
About this news item about genetics and neuroscience study
Author: Jörg Tatzelt
Source: RUB
Contact: Jörg Tatzelt – RUB
Image: The image is credited to AG Tatzelt
Original Research: Closed entry.
Jörg Tatzelt and colleagues ‘ paper,” Implications for Prion Diseases: Implications for Prion Diseases: Topological Confinement by a Membrane Anchor Lowers Phase Separation into Protein Aggregates.” Science
Abstract
Implications for Prion Diseases: Implications for Prion Diseases: Topological Confinement by a Membrane Anchor Lowers Phase Separation into Protein Aggregates
Different neurological disorders exhibit protein aggregation and misfolding. The fundamental mechanisms that cause protein misfolding in the mobile perspective are still largely unknown.
We demonstrate that the two-dimensional confinement imposed by a membrane anchor prevents liquid–liquid phase separation ( LLPS) and protein aggregation and stabilizes the native protein structure.
The expression of anchorless prion protein ( PrP ) is linked to neurodegeneration in transgenic mice and human inherited prion diseases, which suggests that the native PrP’s C-terminal glycosylphosphatidylinositol ( GPI ) anchor prevents the spontaneous formation of neurotoxic and infectious PrP species.
We demonstrate that anchoring to membrane prevents LLPS and PrP formation in a distinct in vitro and in vivo method. Upon discharge from the barrier, PrP undergoes a structural changeover to detergent-insoluble aggregates.
Our research provides a molecular foundation for inherited prion diseases caused by anchorless PrP, and provides an important role for the GPI buoy in preventing unplanned misfolding of PrPC .
