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Updated: Jun 19, 2026

Selection of Aptamers for Amyloid β-Protein, the Causative Agent of Alzheimer's Disease
15:23

Selection of Aptamers for Amyloid β-Protein, the Causative Agent of Alzheimer's Disease

Published on: May 14, 2010

Protein disulfide isomerase dissolves and detoxifies oligomeric assemblies of amyloid beta peptide

Antonio Mele1, Albert Serrano1, Maria C Zabala-Rodriguez1

  • 1Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA.

FEBS Letters
|February 20, 2026
PubMed

Insights

Protein disulfide isomerase (PDI) dissolves toxic amyloid beta (Aβ) oligomers, offering neuroprotection against Alzheimer's disease. This disaggregase activity targets early Aβ aggregates, not fibrils, suggesting therapeutic potential.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Molecular Biology

Background:

  • Alzheimer's disease (AD) is linked to aggregated amyloid beta (Aβ) peptides, which exhibit neurotoxicity and prion-like transmission.
  • Understanding the mechanisms of Aβ aggregation and clearance is crucial for developing AD therapies.

Purpose of the Study:

  • To investigate the disaggregase activity of protein disulfide isomerase (PDI) against different forms of amyloid beta (Aβ).
  • To determine the potential of PDI as a therapeutic agent for Alzheimer's disease by examining its interaction with Aβ oligomers and its effect on cellular toxicity.

Main Methods:

  • Assessing PDI's disaggregase activity on monomeric, oligomeric, and fibrillar forms of Aβ.
  • Evaluating PDI's binding affinity to various Aβ species.
  • Testing the neuroprotective effects of PDI against Aβ-induced toxicity in cellular models.
  • Investigating the impact of S-nitrosylated PDI on Aβ binding and disaggregase activity.

Main Results:

  • PDI demonstrated significant disaggregase activity against oligomeric Aβ but not fibrillar Aβ.
  • PDI did not bind monomeric Aβ, indicating its mechanism involves reversing early-stage oligomers.
  • Cells treated with both PDI and oligomeric Aβ were protected from Aβ-induced neurotoxicity.
  • S-nitrosylated PDI, linked to neurodegeneration, lost its ability to bind oligomeric Aβ and its neuroprotective disaggregase activity.

Conclusions:

  • PDI possesses disaggregase activity specifically against neurotoxic oligomeric forms of Aβ.
  • PDI's interaction with Aβ oligomers offers a potential therapeutic strategy for Alzheimer's disease.
  • Modulation of PDI activity, particularly avoiding S-nitrosylation, could be key for its neuroprotective role.
Keywords:
Alzheimer's diseasechaperoneconditional disorderdisaggregaseprotein disulfide isomerase

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