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Updated: Jun 16, 2026
08:59
Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis
Published on: July 16, 2021
Calcium dysregulation in amyotrophic lateral sclerosis
Julian Grosskreutz1, Ludo Van Den Bosch, Bernhard U Keller
1Dept. of Neurology, Friedrich-Schiller University Hospital Jena, Erlanger Allee 101, 07747 Jena, Germany. julian.grosskreutz@med.uni-jena.de
Cell Calcium
|February 2, 2010
Summary
Amyotrophic lateral sclerosis (ALS) involves motor neuron death due to calcium dysregulation. A toxic shift in the endoplasmic reticulum-mitochondria calcium cycle (ERMCC) is proposed as a key mechanism driving neurodegeneration.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration.
- Key pathological hallmarks include organelle fragmentation, oxidative stress, mitochondrial calcium overload, and protein aggregation.
- Specific motor neuron populations with reduced calcium-buffering capacity are particularly susceptible.
Purpose of the Study:
- To review the role of calcium dysregulation in motor neuron degeneration in ALS.
- To introduce the "toxic shift of Ca2+" hypothesis within the endoplasmic reticulum-mitochondria calcium cycle (ERMCC).
- To identify potential molecular targets for novel neuroprotective therapies.
Main Methods:
- Review of existing literature on ALS pathogenesis and calcium signaling.
- Analysis of the interplay between endoplasmic reticulum and mitochondria in calcium homeostasis.
- Discussion of excitotoxicity mediated by AMPA receptors in ALS.
Main Results:
- Chronic excitotoxicity via Ca2+-permeable AMPA receptors contributes to intracellular Ca2+ dysregulation in ALS.
- This dysregulation leads to endoplasmic reticulum Ca2+ depletion and mitochondrial Ca2+ overload.
- Riluzole, a current treatment, may exert its effects by reducing glutamatergic input.
Conclusions:
- A "toxic shift of Ca2+" within the ERMCC is hypothesized as a central mechanism in ALS motor neuron death.
- Targeting the ERMCC offers potential for developing new neuroprotective strategies for ALS.
- Further research into ERMCC-modulating therapies is warranted.
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