This AOP is open for adoption and licensed under the BY-SA license. The BY-SA license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.
AOP: 26
Title
Calcium-mediated neuronal ROS production and energy imbalance
Short name
Graphical Representation
Point of Contact
Contributors
- Lyle Burgoon
- Erik Mylroie
Coaches
OECD Information Table
| OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
|---|---|---|---|---|
This AOP was last modified on February 25, 2025 10:45
Revision dates for related pages
| Page | Revision Date/Time |
|---|---|
| Inhibition, Ca++ ATPase | September 16, 2017 10:14 |
| Increase, Ca++ (intracellular) | September 16, 2017 10:14 |
| Mitochondrial electron transport chain, disrupted | January 07, 2026 11:28 |
| Mitochondrial ATP production, decreased | October 16, 2025 02:35 |
| Decreased, Nitric Oxide | September 16, 2017 10:14 |
| Decreased, Long-term potentiation (LTP) | September 16, 2017 10:14 |
| Increase, Oxidative Stress | February 11, 2026 07:05 |
| Increase, Reactive oxygen species | June 12, 2025 01:27 |
| Inhibition, Ca++ ATPase leads to Increase, Ca++ (intracellular) | December 03, 2016 16:37 |
| Increase, Ca++ (intracellular) leads to Mitochondrial electron transport chain, disrupted | December 03, 2016 16:37 |
| Mitochondrial electron transport chain, disrupted leads to Mitochondrial ATP production, decreased | December 03, 2016 16:37 |
| Mitochondrial electron transport chain, disrupted leads to Increase, ROS | February 25, 2025 10:35 |
| Decreased, Nitric Oxide leads to Decreased, Long-term potentiation (LTP) | December 03, 2016 16:37 |
| Increase, ROS leads to Decreased, Nitric Oxide | February 25, 2025 10:36 |
| Increase, ROS leads to Increase, Oxidative Stress | August 02, 2024 15:40 |
Abstract
Chemicals may lead to neurotoxicity through the inhibition of calcium ATPase activity, leading to increased intracellular calcium, increased ROS, and energy imbalance. This may lead to impaired nuerotransmission and oxidative neuronal damage.
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
| Type | Event ID | Title | Short name |
|---|
| MIE | 51 | Inhibition, Ca++ ATPase | Inhibition, Ca++ ATPase |
| KE | 50 | Increase, Ca++ (intracellular) | Increase, Ca++ (intracellular) |
| KE | 178 | Mitochondrial electron transport chain, disrupted | Mitochondrial electron transport chain, disrupted |
| KE | 40 | Mitochondrial ATP production, decreased | Mitochondrial ATP production, decreased |
| KE | 1115 | Increase, Reactive oxygen species | Increase, ROS |
| KE | 193 | Decreased, Nitric Oxide | Decreased, Nitric Oxide |
| KE | 166 | Decreased, Long-term potentiation (LTP) | Decreased, Long-term potentiation (LTP) |
| AO | 1392 | Increase, Oxidative Stress | Increase, Oxidative Stress |
Relationships Between Two Key Events (Including MIEs and AOs)
| Title | Adjacency | Evidence | Quantitative Understanding |
|---|
Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
Overall Assessment of the AOP
Consider the following criteria (may include references to KE Relationship pages): 1. concordance of dose-response relationships; 2. temporal concordance among the key events and adverse effect; 3. strength, consistency, and specificity of association of adverse effect and initiating event; 4. biological plausibility, coherence, and consistency of the experimental evidence; 5. alternative mechanisms that logically present themselves and the extent to which they may distract from the postulated AOP. It should be noted that alternative mechanisms of action, if supported, require a separate AOP; 6. uncertainties, inconsistencies and data gaps.