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Updated: Sep 18, 2025
09:44
Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo
Published on: June 2, 2019
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Humanin variants aggregate to produce different fibril morphologies.
Daniel L Morris1, Sarah B Nyenhuis2, James M Gruschus1
1Laboratory of Structural Biology, Biochemistry and Biophysics Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
The Journal of Biological Chemistry
|June 21, 2025
Summary
Humanin (HN) forms amyloid-like fibrils, revealing its molecular structure. This beta-sheet structure is crucial for HN
Area of Science:
- Biochemistry and Molecular Biology
- Structural Biology
- Cellular Biology
Background:
- Humanin (HN) is an endogenous peptide with demonstrated cytoprotective properties.
- HN's therapeutic potential for diseases, aging, and athletic performance is recognized, yet its molecular structure and interactions remain poorly understood.
- HN inhibits apoptosis, partly through interactions with BCL-2 family proteins like BAX.
Purpose of the Study:
- To elucidate the molecular structure of humanin (HN).
- To investigate the mechanism of HN's interaction with its protein partners.
- To characterize the secondary structure properties and fibrillization of HN.
Main Methods:
- Amyloid-like β-sheet fibrillization of HN was induced and characterized.
- Transmission electron microscopy (TEM) and biophysical techniques were employed to analyze HN's secondary structure.
- Key HN mutants were identified and their effects on fibrillization were assessed.
Main Results:
- Humanin (HN) undergoes amyloid-like β-sheet fibrillization.
- Mutants with inhibited β-sheet fibrillization were linked to impaired in vitro secretion and membrane interactions.
- Successful β-sheet structural transitions are essential for HN's anti-apoptotic activity via BCL-2 family protein interactions.
Conclusions:
- The β-sheet structure of humanin (HN) is critical for its biological functions, including membrane interactions and apoptosis inhibition.
- Understanding HN fibrillization provides insights into its mechanism of action and potential therapeutic administration.
- Further research into HN's structural dynamics can optimize its therapeutic applications.
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