Summary
Amyloidogenesis is the process by which proteins assemble into ordered, insoluble fibrils with a cross-β structure. Prion propagation is a specific subset where the misfolded state becomes infectious and self-propagating.
Key Points
- 1Amyloid fibrils have cross-β structure with steric zippers
- 2Prions are infectious proteins that template their conformation
- 3Prion strains arise from distinct conformations of the same sequence
- 4Prion-like mechanisms drive progression of major neurodegenerative diseases
Amyloidogenesis and prion propagation represent extremes of protein misfolding where alternative conformations become self-perpetuating.
Amyloid Structure
Amyloid fibrils share a common cross-β architecture:
The Cross-β Spine
- β-strands run perpendicular to the fibril axis
Steric Zippers
At the atomic level, amyloid is stabilized by steric zippers:
Prion Propagation
Prion diseases represent a unique form of pathology where misfolding is infectious.
The Protein-Only Hypothesis
Stanley Prusiner's revolutionary concept:
- The pathogenic agent is a protein (PrP^Sc), not a virus or bacterium
- PrP^Sc acts as a conformational template
The Prion Cycle
4. Fragmentation creates new seeds
Prion Strains
A remarkable phenomenon demonstrating conformational diversity:
- A single amino acid sequence can adopt multiple distinct prion conformations
Species Barriers
Prion transmission between species is limited by:
Prion-Like Mechanisms in Common Diseases
The prion paradigm now extends beyond classical prion diseases:
- Alzheimer's: Aβ and tau spread in prion-like fashion
- Parkinson's: α-synuclein propagates between neurons
- ALS: SOD1 and TDP-43 show prion-like properties
This "prion-like" spreading explains the stereotyped progression patterns of neurodegenerative diseases.