Tyramine and Amyloid Beta 42: A Toxic Synergy
Implicated in various diseases including Parkinson’s disease, Huntington’s disease, migraines, schizophrenia and increased blood pressure, tyramine plays a crucial role as a neurotransmitter in the synaptic cleft by reducing serotonergic and dopaminergic signaling through a trace amine-associated re...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-05-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/8/6/145 |
| _version_ | 1797566542786854912 |
|---|---|
| author | Sudip Dhakal Ian Macreadie |
| author_facet | Sudip Dhakal Ian Macreadie |
| author_sort | Sudip Dhakal |
| collection | DOAJ |
| description | Implicated in various diseases including Parkinson’s disease, Huntington’s disease, migraines, schizophrenia and increased blood pressure, tyramine plays a crucial role as a neurotransmitter in the synaptic cleft by reducing serotonergic and dopaminergic signaling through a trace amine-associated receptor (TAAR1). There appear to be no studies investigating a connection of tyramine to Alzheimer’s disease. This study aimed to examine whether tyramine could be involved in AD pathology by using <i>Saccharomyces cerevisiae</i> expressing Aβ42. <i>S. cerevisiae</i> cells producing native Aβ42 were treated with different concentrations of tyramine, and the production of reactive oxygen species (ROS) was evaluated using flow cytometric cell analysis. There was dose-dependent ROS generation in wild-type yeast cells with tyramine. In yeast producing Aβ42, ROS levels generated were significantly higher than in controls, suggesting a synergistic toxicity of Aβ42 and tyramine. The addition of exogenous reduced glutathione (GSH) was found to rescue the cells with increased ROS, indicating depletion of intracellular GSH due to tyramine and Aβ42. Additionally, tyramine inhibited the respiratory growth of yeast cells producing GFP-Aβ42, while there was no growth inhibition when cells were producing GFP. Tyramine was also demonstrated to cause increased mitochondrial DNA damage, resulting in the formation of petite mutants that lack respiratory function. These findings indicate that there can be a detrimental synergy between Aβ42 and tyramine, which could be considered in Alzheimer’s disease. This work also demonstrates the utility of yeast as a model for studying toxic agents such as Aβ42, tyramine, and agents that might exacerbate AD pathology. |
| first_indexed | 2024-03-10T19:28:22Z |
| format | Article |
| id | doaj.art-12e169bc01b94597b8fa6b535273ddf6 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T19:28:22Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-12e169bc01b94597b8fa6b535273ddf62023-11-20T02:18:51ZengMDPI AGBiomedicines2227-90592020-05-018614510.3390/biomedicines8060145Tyramine and Amyloid Beta 42: A Toxic SynergySudip Dhakal0Ian Macreadie1School of Science, RMIT University, Bundoora, VIC 3083, AustraliaSchool of Science, RMIT University, Bundoora, VIC 3083, AustraliaImplicated in various diseases including Parkinson’s disease, Huntington’s disease, migraines, schizophrenia and increased blood pressure, tyramine plays a crucial role as a neurotransmitter in the synaptic cleft by reducing serotonergic and dopaminergic signaling through a trace amine-associated receptor (TAAR1). There appear to be no studies investigating a connection of tyramine to Alzheimer’s disease. This study aimed to examine whether tyramine could be involved in AD pathology by using <i>Saccharomyces cerevisiae</i> expressing Aβ42. <i>S. cerevisiae</i> cells producing native Aβ42 were treated with different concentrations of tyramine, and the production of reactive oxygen species (ROS) was evaluated using flow cytometric cell analysis. There was dose-dependent ROS generation in wild-type yeast cells with tyramine. In yeast producing Aβ42, ROS levels generated were significantly higher than in controls, suggesting a synergistic toxicity of Aβ42 and tyramine. The addition of exogenous reduced glutathione (GSH) was found to rescue the cells with increased ROS, indicating depletion of intracellular GSH due to tyramine and Aβ42. Additionally, tyramine inhibited the respiratory growth of yeast cells producing GFP-Aβ42, while there was no growth inhibition when cells were producing GFP. Tyramine was also demonstrated to cause increased mitochondrial DNA damage, resulting in the formation of petite mutants that lack respiratory function. These findings indicate that there can be a detrimental synergy between Aβ42 and tyramine, which could be considered in Alzheimer’s disease. This work also demonstrates the utility of yeast as a model for studying toxic agents such as Aβ42, tyramine, and agents that might exacerbate AD pathology.https://www.mdpi.com/2227-9059/8/6/145tyramineamyloid-betaAlzheimer’s diseaseoxidative stressyeastpetite mutant |
| spellingShingle | Sudip Dhakal Ian Macreadie Tyramine and Amyloid Beta 42: A Toxic Synergy Biomedicines tyramine amyloid-beta Alzheimer’s disease oxidative stress yeast petite mutant |
| title | Tyramine and Amyloid Beta 42: A Toxic Synergy |
| title_full | Tyramine and Amyloid Beta 42: A Toxic Synergy |
| title_fullStr | Tyramine and Amyloid Beta 42: A Toxic Synergy |
| title_full_unstemmed | Tyramine and Amyloid Beta 42: A Toxic Synergy |
| title_short | Tyramine and Amyloid Beta 42: A Toxic Synergy |
| title_sort | tyramine and amyloid beta 42 a toxic synergy |
| topic | tyramine amyloid-beta Alzheimer’s disease oxidative stress yeast petite mutant |
| url | https://www.mdpi.com/2227-9059/8/6/145 |
| work_keys_str_mv | AT sudipdhakal tyramineandamyloidbeta42atoxicsynergy AT ianmacreadie tyramineandamyloidbeta42atoxicsynergy |