Related Experiment Video

Updated: May 29, 2026

Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster
10:26

Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster

Published on: March 12, 2018

Amyloid-β-induced synapse damage is mediated via cross-linkage of cellular prion proteins

Clive Bate1, Alun Williams2

  • 1Department of Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, United Kingdom.

The Journal of Biological Chemistry
|September 9, 2011
PubMed

Insights

Amyloid-beta (Aβ) oligomers cause synapse damage by binding to cellular prion protein (PrP(C)). This interaction activates cytoplasmic phospholipase A(2) (cPLA(2)), leading to neuronal dysfunction in Alzheimer disease.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Cellular prion protein (PrP(C)) is abundant at synapses.
  • Amyloid-beta (Aβ) oligomers are implicated in Alzheimer disease dementia.
  • PrP(C) acts as a receptor for Aβ oligomers.

Purpose of the Study:

  • To investigate the mechanism by which Aβ oligomers induce synapse damage.
  • To determine the role of PrP(C) in Aβ-mediated synapse pathology.
  • To elucidate the signaling pathway involving cPLA(2) activation.

Main Methods:

  • Using cultured neurons (Prnp knock-out and wild-type).
  • Employing Aβ oligomers and PrP(C) in cell cultures.
  • Utilizing biochemical assays (filtration, non-denaturing gels) and microscopy to detect protein interactions and localization.
  • Investigating the activation and translocation of cytoplasmic phospholipase A(2) (cPLA(2)).

Main Results:

  • Aβ oligomers caused PrP(C)-dependent synapse damage in cultured neurons.
  • Exogenous PrP(C) enhanced Aβ-induced synapse damage in Prnp knock-out neurons.
  • Aβ oligomers activated synaptic cPLA(2) and promoted its translocation to lipid rafts in Prnp wild-type neurons, forming a complex with Aβ and PrP(C).
  • Aβ oligomers were shown to cross-link PrP(C).
  • Antibody-mediated cross-linking of PrP(C) mimicked Aβ effects, activating cPLA(2) and causing synapse damage.

Conclusions:

  • Aβ oligomer-induced synapse damage is mediated by PrP(C).
  • PrP(C) cross-linking by Aβ oligomers triggers aberrant cPLA(2) activation, leading to synapse damage.
  • This pathway represents a key mechanism in Alzheimer disease pathogenesis.

More Related Videos

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans12:57

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans

Published on: January 8, 2015

Preparation of Oligomeric β-amyloid1-42 and Induction of Synaptic Plasticity Impairment on Hippocampal Slices04:41

Preparation of Oligomeric β-amyloid1-42 and Induction of Synaptic Plasticity Impairment on Hippocampal Slices

Published on: July 14, 2010

Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...