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Related Experiment Videos

Data-driven modeling of mitochondrial dysfunction in Alzheimer's disease.

Patrick Toglia1, Angelo Demuro2, Don-On Daniel Mak3

  • 1Department of Physics, University of South Florida, Tampa, FL 33620, USA.

Cell Calcium
|September 25, 2018
PubMed
Summary

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Cell calcium·2025

Intracellular amyloid-beta (Aβ) oligomers impair neuronal function by disrupting calcium homeostasis, leading to mitochondrial dysfunction and cell death in Alzheimer

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biophysics

Background:

  • Intracellular accumulation of amyloid-beta (Aβ) oligomers is implicated in early Alzheimer's disease (AD).
  • Aβ oligomers disrupt neuronal calcium (Ca2+) homeostasis, but downstream effects remain unclear.
  • Understanding Ca2+-dependent pathways affected by Aβ is crucial for AD research.

Purpose of the Study:

  • To investigate how intracellular Aβ42 oligomers impact neuronal function and mitochondrial health.
  • To model the Ca2+ signaling pathways affected by Aβ42.
  • To elucidate the mechanisms of Aβ42-induced cytotoxicity.

Main Methods:

  • Multiscale modeling of inositol 1,4,5-trisphosphate receptor (IP3R) kinetics.
  • Patch-clamp electrophysiology and fluorescence imaging of Ca2+ responses.
Keywords:
Alzheimer's diseaseCa(2+) dyshomeostasisIntracellular β amyloidMitochondrial dysfunction

Related Experiment Videos

  • Quantification of Ca2+ release from the endoplasmic reticulum induced by Aβ42.

    • Main Results:

    • Aβ42 oligomers induce cytotoxicity by impairing mitochondrial function.
    • Pathological Ca2+ uptake by mitochondria leads to reduced membrane potential, lower ATP, and increased reactive oxygen species (ROS).
    • EGTA, a Ca2+ buffer, abrogates Aβ42 cytotoxicity, restoring mitochondrial function.

    Conclusions:

    • Intracellular Aβ42 oligomers trigger a cascade leading to mitochondrial dysfunction and cell death.
    • Disruption of Ca2+ homeostasis is a key mechanism in Aβ42 toxicity.
    • Targeting Ca2+ signaling pathways may offer therapeutic strategies for Alzheimer's disease.