The alpha-synuclein Preformed Fibrils (PFF) model is a powerful experimental system for studying Parkinson's disease (PD) and related α-synucleinopathies. Unlike transgenic models that overexpress mutant protein, the PFF model exploits the prion-like property of α-synuclein to induce aggregation of endogenous protein.
Mechanism of Pathology
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The alpha-synuclein Preformed Fibrils (PFF) model is a powerful experimental system for studying Parkinson's disease (PD) and related α-synucleinopathies. Unlike transgenic models that overexpress mutant protein, the PFF model exploits the prion-like property of α-synuclein to induce aggregation of endogenous protein.
Mechanism of Pathology
Mermaid diagram (expand to render)
Prion-Like Propagation
The PFF model is based on the self-propagating nature of misfolded α-synuclein:
Seeding: Exogenous synthetic α-synuclein fibrils (PFF) are internalized by neurons
Template-directed misfolding: PFF serve as templates for endogenous [alpha-synuclein](/proteins/alpha-synuclein) to adopt the β-sheet conformation
Oligomerization: Initial soluble oligomers form, then mature into insoluble fibrils
Propagation: Aggregated species can transmit between connected neurons
Cellular Pathways Involved
Endocytosis: PFF enter cells via clathrin-mediated endocytosis
Autophagy: Both macroautophagy and chaperone-mediated autophagy process aggregates
Tubulin polymerization: PFF transport along microtubules to the soma
Synaptic transmission: Inter-neuronal transfer via synaptic vesicles