The Molecular Assembly of Amyloid Aβ Controls Its Neurotoxicity and Binding to Cellular Proteins
2011

How Amyloid Peptides Affect Brain Cells

publication 10 minutes Evidence: moderate

Author Information

Author(s): Claudia Manzoni, Laura Colombo, Paolo Bigini, Valentina Diana, Alfredo Cagnotto, Massimo Messa, Monica Lupi, Valentina Bonetto, Mauro Pignataro, Cristina Airoldi, Erika Sironi, Alun Williams, Mario Salmona

Primary Institution: Mario Negri Institute for Pharmacological Research, Milan, Italy

Hypothesis

The study investigates the relationship between the molecular assembly of amyloid Aβ peptides and their neurotoxicity.

Conclusion

The study concludes that Aβ toxic species can cross cell membranes and bind to various proteins, leading to multiple pathways of toxicity.

Supporting Evidence

  • Aβ peptides were shown to cross the plasma membrane and bind to various internal proteins.
  • The study established a structure-function relationship between peptide aggregation state and toxic properties.
  • Different Aβ preparations exhibited varying levels of toxicity and protein binding capacity.
  • The findings suggest that multiple proteins can act as receptors for Aβ, leading to diverse toxic effects.

Takeaway

This study shows that certain proteins in the brain can be harmed by sticky substances called amyloid peptides, which are linked to Alzheimer's disease.

Methodology

The toxicity of Aβ 1–40 and Aβ 1–42 was evaluated using the N2a cell line, and the binding of Aβ to cellular proteins was analyzed through various biochemical techniques.

Limitations

The study primarily uses a single cell line (N2a) which may not fully represent the complexity of human neuronal responses.

Statistical Information

P-Value

p<0.001

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0024909

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