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Related Experiment Video

Updated: Nov 3, 2025

Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins

Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins

Published on: August 15, 2017

PSD-95 protects synapses from β-amyloid.

Kim Dore¹, Zachary Carrico¹, Stephanie Alfonso¹

¹Center for Neural Circuits and Behavior, Department of Neuroscience and Section for Neurobiology, Division of Biology, University of California, San Diego, San Diego, CA 92093, USA.

|June 2, 2021

Summary

This summary is machine-generated.

Increased PSD-95 protein protects synapses from beta-amyloid toxicity by stabilizing NMDA receptor interactions. This finding suggests targeting PSD-95 could be a therapeutic strategy for Alzheimer's disease.

Keywords:

ABHD17 Alzheimer's disease FRET-FLIM Fluorescence lifetime imaging PSD-95 palmitoylation Palmostatin B Synapto-toxic signaling ion-flux independent neuroprotection spine density

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

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Published on: June 17, 2015

Area of Science:

Neuroscience
Molecular Biology
Cell Biology

Background:

Beta-amyloid (Aβ) accumulation is a hallmark of Alzheimer's disease.
Aβ impairs excitatory synapses through mechanisms involving NMDA receptor (NMDAR) function.
The precise molecular pathways linking Aβ to synaptic dysfunction remain incompletely understood.

Purpose of the Study:

To elucidate the role of the synaptic scaffolding protein PSD-95 in mediating Aβ-induced synaptic depression.
To investigate how PSD-95 levels influence NMDAR function and synaptic integrity in the presence of Aβ.

Main Methods:

Utilized electrophysiological recordings in brain tissue.
Investigated protein-protein interactions involving NMDAR C-terminal domains (CTD) and protein phosphatase 1 (PP1).
Examined the effects of altered PSD-95 levels (endogenous or overexpressed) and pharmacological inhibition of depalmitoylation.

Main Results:

Increased PSD-95 levels were found to block the detrimental effects of Aβ on excitatory synapses.
Aβ alters NMDAR CTD conformation and its interaction with PP1, leading to synaptic weakening.
Elevated PSD-95 prevents these Aβ-induced molecular changes at the NMDAR, preserving synaptic function.
Pharmacological inhibition of PSD-95 depalmitoylation increased synaptic PSD-95 and rescued Aβ-induced deficits.

Conclusions:

Elevated synaptic PSD-95 confers protection against Aβ-induced synaptic toxicity.
Low synaptic PSD-95 levels may indicate synapse vulnerability in Alzheimer's disease.
Modulating PSD-95 levels, potentially via depalmitoylation inhibition, represents a promising therapeutic strategy for Alzheimer's disease.