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Alzheimer's Aβ interacts with cellular prion protein inducing neuronal membrane damage and synaptotoxicity

Christian Peters1, María Paz Espinoza1, Scarlet Gallegos1

  • 1Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Concepción, Chile.

Neurobiology of Aging
|January 21, 2015
PubMed

Insights

Alzheimer's disease involves β-amyloid (Aβ) oligomers interacting with cellular prion protein (PrPc) on neurons. This interaction contributes to Aβ toxicity, synaptic failure, and may offer new therapeutic targets.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Cell Biology

Background:

  • Alzheimer's disease (AD) is characterized by β-amyloid (Aβ) peptide accumulation in the brain.
  • Recent research suggests Aβ oligomers (Aβo) interact with the cellular prion protein (PrPc).
  • This interaction may mediate Aβ's toxic effects in synaptic regions.

Purpose of the Study:

  • To investigate the role of PrPc in Aβo-induced neurotoxicity.
  • To determine if Aβo binds to PrPc on the neuronal membrane.
  • To explore therapeutic strategies targeting the Aβo-PrPc interaction.

Main Methods:

  • Enzymatic cleavage of PrPc from neuronal membranes using Phospholipase C.
  • Utilizing an anti-PrP antibody (6D11) to block Aβo-PrPc interaction.
  • Measuring membrane conductance, intracellular calcium levels, and synaptic vesicle release.

Main Results:

  • Aβo binds to PrPc on the neuronal membrane, contributing to Aβ toxicity.
  • Cleavage of PrPc or antibody blockade reduced Aβo association with neurons.
  • The anti-PrP antibody inhibited Aβo-induced increases in membrane conductance and intracellular calcium.

Conclusions:

  • PrPc mediates Aβo binding to neurons and plays a role in Aβo-induced membrane damage.
  • PrPc is involved in Aβo-induced calcium influx and synaptic vesicle release, leading to synaptic failure.
  • Targeting the Aβo-PrPc interaction presents a potential therapeutic avenue for Alzheimer's disease.
Keywords:
AlzheimerBeta amyloidPrionSynaptic toxicity

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