Glycine Zipper Motif in β-Amyloid and Its Role in Toxicity
Author Information
Author(s): Virginia Fonte, Vishantie Dostal, Christine M. Roberts, Patrick Gonzales, Pascale Lacor, Jordi Magrane, Natalie Dingwell, Emily Y. Fan, Michael A. Silverman, Gretchen H. Stein, Christopher D. Link
Primary Institution: Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA
Hypothesis
The glycine zipper motif in the β-amyloid peptide drives the formation of toxic oligomers.
Conclusion
The glycine zipper motif in the C-terminal portion of β-amyloid is crucial for the formation of toxic oligomers, and disrupting this motif can reduce toxicity.
Supporting Evidence
- A Gly37Leu substitution in β-amyloid significantly reduced toxicity in multiple models.
- Compounds designed to disrupt the glycine zipper could have therapeutic potential.
- Aβ Gly37Leu was shown to be anti-toxic in both neuronal cell lines and C. elegans models.
- Second site substitutions in Aβ restored toxicity, supporting the glycine zipper model.
Takeaway
The study shows that a specific part of the β-amyloid protein helps it become toxic, and changing that part can make it less harmful.
Methodology
The study used neuronal cell lines, primary neurons, and a transgenic C. elegans model to test the toxicity of β-amyloid variants.
Limitations
The study does not provide direct evidence linking reduced toxicity to membrane conductance changes.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website