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Preparation of Oligomeric &#946;-amyloid1-42 and Induction of Synaptic Plasticity Impairment on Hippocampal Slices
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Soluble amyloid-β precursor peptide does not regulate GABAB receptor activity.

Pascal Dominic Rem1, Vita Sereikaite2, Diego Fernández-Fernández1

  • 1Department of Biomedicine, Pharmazentrum, University of Basel, Basel, Switzerland.

Elife
|January 23, 2023
PubMed
Summary
This summary is machine-generated.

Amyloid precursor protein (APP) peptide APP17 binds GABAB receptors (GBRs) but does not activate them. This suggests secreted APP (sAPP) influences neuronal activity via other receptors, not GBRs.

Keywords:
G protein-coupled receptorsGABABmouseneurosciencesoluble amyloid-β precursor protein

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Secreted amyloid precursor protein (sAPP) modulates neuronal activity by interacting with cell surface receptors.
  • Previous studies suggested sAPP and a derived peptide (APP17) bind to GABAB receptors (GBRs) and mimic their inhibitory effects, proposing sAPP activates GBRs.

Purpose of the Study:

  • To investigate whether APP17 and sAPP functionally activate classical GABAB receptor signaling pathways.
  • To determine if APP17 acts as a functional ligand for GBRs.

Main Methods:

  • Binding assays to confirm APP17 affinity for GBRs.
  • Biochemical and electrophysiological analyses in heterologous cells to assess GBR activity.
  • In vitro and in vivo experiments to evaluate APP17 effects on synaptic GBR localization, GBR-activated currents, neurotransmitter release, and neuronal activity.

Main Results:

  • APP17 demonstrated nanomolar affinity binding to GBRs.
  • Biochemical and electrophysiological studies revealed APP17 does not influence GBR activity in heterologous cells.
  • APP17 did not affect synaptic GBR localization, GBR-activated K+ currents, neurotransmitter release, or neuronal activity in vitro or in vivo.

Conclusions:

  • APP17 is not a functional ligand for GABAB receptors.
  • The findings indicate that secreted APP (sAPP) exerts its neuronal effects through mechanisms independent of GABAB receptor activation.