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Fibrils from synthetic amyloid-related peptides enhance development of experimental AA-amyloidosis in mice
K Ganowiak1, P Hultman, U Engström
1Department of Pathology, University Hospital, Linköping, Sweden.
Abstract:
Amyloid enhancing factor is an incompletely characterized activity of extracts from many amyloid-containing tissues and which greatly shortens the preamyloidotic phase during experimental induction of AA-amyloidosis. In this communication we show that amyloid-like fibrils made in vitro from synthetic peptides, corresponding to segments of amyloid fibril proteins, have amyloid enhancing factor-like activity. Thus, there is a possibility that amyloid enhancing factor activity depends on small fibrils serving as nucleation centers for fibril elongation.
Insights
Amyloid enhancing factor (AEF) activity, which accelerates amyloidosis, may stem from small, synthetic amyloid-like fibrils. These fibrils act as nucleation centers, promoting the elongation of amyloid deposits in experimental models.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathology
Background:
- Amyloid enhancing factor (AEF) is a poorly understood activity found in amyloid-rich tissues.
- AEF significantly reduces the pre-amyloid phase in experimental AA-amyloidosis induction.
- The precise molecular nature of AEF remains elusive.
Purpose of the Study:
- To investigate the potential role of amyloid-like fibrils in AEF activity.
- To determine if synthetic amyloid fibrils exhibit AEF-like properties.
- To explore the mechanism by which AEF might accelerate amyloidogenesis.
Main Methods:
- In vitro synthesis of amyloid-like fibrils using peptide segments of amyloid fibril proteins.
- Assay of the synthesized fibrils for amyloid enhancing factor-like activity.
- Experimental induction of AA-amyloidosis to evaluate the effect of synthetic fibrils.
Main Results:
- Synthetic amyloid-like fibrils, created in vitro, demonstrated AEF-like activity.
- These synthetic fibrils were derived from segments of known amyloid fibril proteins.
- The presence of these fibrils shortened the preamyloidotic phase in experimental AA-amyloidosis.
Conclusions:
- Amyloid enhancing factor activity may be attributed to the presence of small amyloid-like fibrils.
- These fibrils likely function as nucleation centers, facilitating amyloid fibril elongation.
- This finding suggests a potential mechanism for AEF's role in accelerating amyloidosis.