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Updated: Mar 13, 2026

Rapid Generation of Amyloid from Native Proteins In vitro
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Published on: December 5, 2013

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Pre-amyloid oligomers budding:a metastatic mechanism of proteotoxicity

Fabrizio Bernini1, Daniele Malferrari1, Marcello Pignataro1,2

  • 1Department of Chemical and Geological Sciences, University of Modena &Reggio Emilia, Modena, Italy.

Scientific Reports
|October 25, 2016
PubMed

Insights

Misfolded proteins form toxic aggregates in aging and disease. This study reveals how these aggregates mature, spread, and how immunotherapies impact this process, offering new insights for potential treatments.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Neuroscience

Background:

  • Misfolded protein aggregates, such as amyloid fibers, are central to neurodegenerative diseases and aging.
  • The precise mechanisms of proteotoxicity, aggregate formation, and spread are not fully understood, hindering therapeutic development.

Purpose of the Study:

  • To elucidate the dynamic changes in amyloid aggregate formation, maturation, and dissemination.
  • To investigate the impact of immunotherapy on these processes.

Main Methods:

  • Utilized atomic force microscopy (AFM) for high-resolution imaging of amyloid aggregate dynamics.
  • Employed a reductionist approach to study temporal and spatial changes in fiber formation.
  • Simulated immunotherapy interventions using anti-fiber and anti-pre-amyloid oligomer antibodies.

Main Results:

  • Demonstrated the maturation pathway from pre-amyloid oligomers (PAOs) to protofibrils and amyloid fibers.
  • Observed that amyloid fibers can fragment into PAOs, which can then migrate and invade neighboring structures.
  • Showed that while both anti-fiber and anti-PAO antibodies fragment fibers, anti-fiber antibodies can promote PAO migration.

Conclusions:

  • Provided evidence for the mechanisms underlying misfolded protein maturation and propagation.
  • Highlighted the dual effects of immunotherapy interventions, with potential to both resolve and disseminate amyloid pathology.

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