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Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine
Bipolar disorder’s core feature is the pathological disturbances in mood, often accompanied by disrupted thinking and behavior. Its complex and heterogeneous etiology implies that a range of inherited and environmental factors are involved. This heterogeneity and poorly understood neurobiology pose...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618096/ https://www.ncbi.nlm.nih.gov/pubmed/37386057 http://dx.doi.org/10.1038/s41380-023-02134-8 |
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author | Khanra, Sourav Reddy, Preethi Giménez-Palomo, Anna Park, Chun Hui J. Panizzutti, Bruna McCallum, Madeleine Arumugham, Shyam Sundar Umesh, Shreekantiah Debnath, Monojit Das, Basudeb Venkatasubramanian, Ganesan Ashton, Melanie Turner, Alyna Dean, Olivia M. Walder, Ken Vieta, Eduard Yatham, Lakshmi N. Pacchiarotti, Isabella Reddy, Y. C. Janardhan Goyal, Nishant Kesavan, Muralidharan Colomer, Lluc Berk, Michael Kim, Jee Hyun |
author_facet | Khanra, Sourav Reddy, Preethi Giménez-Palomo, Anna Park, Chun Hui J. Panizzutti, Bruna McCallum, Madeleine Arumugham, Shyam Sundar Umesh, Shreekantiah Debnath, Monojit Das, Basudeb Venkatasubramanian, Ganesan Ashton, Melanie Turner, Alyna Dean, Olivia M. Walder, Ken Vieta, Eduard Yatham, Lakshmi N. Pacchiarotti, Isabella Reddy, Y. C. Janardhan Goyal, Nishant Kesavan, Muralidharan Colomer, Lluc Berk, Michael Kim, Jee Hyun |
author_sort | Khanra, Sourav |
collection | PubMed |
description | Bipolar disorder’s core feature is the pathological disturbances in mood, often accompanied by disrupted thinking and behavior. Its complex and heterogeneous etiology implies that a range of inherited and environmental factors are involved. This heterogeneity and poorly understood neurobiology pose significant challenges to existing drug development paradigms, resulting in scarce treatment options, especially for bipolar depression. Therefore, novel approaches are needed to discover new treatment options. In this review, we first highlight the main molecular mechanisms known to be associated with bipolar depression–mitochondrial dysfunction, inflammation and oxidative stress. We then examine the available literature for the effects of trimetazidine in said alterations. Trimetazidine was identified without a priori hypothesis using a gene-expression signature for the effects of a combination of drugs used to treat bipolar disorder and screening a library of off-patent drugs in cultured human neuronal-like cells. Trimetazidine is used to treat angina pectoris for its cytoprotective and metabolic effects (improved glucose utilization for energy production). The preclinical and clinical literature strongly support trimetazidine’s potential to treat bipolar depression, having anti-inflammatory and antioxidant properties while normalizing mitochondrial function only when it is compromised. Further, trimetazidine’s demonstrated safety and tolerability provide a strong rationale for clinical trials to test its efficacy to treat bipolar depression that could fast-track its repurposing to address such an unmet need as bipolar depression. |
format | Online Article Text |
id | pubmed-10618096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106180962023-11-02 Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine Khanra, Sourav Reddy, Preethi Giménez-Palomo, Anna Park, Chun Hui J. Panizzutti, Bruna McCallum, Madeleine Arumugham, Shyam Sundar Umesh, Shreekantiah Debnath, Monojit Das, Basudeb Venkatasubramanian, Ganesan Ashton, Melanie Turner, Alyna Dean, Olivia M. Walder, Ken Vieta, Eduard Yatham, Lakshmi N. Pacchiarotti, Isabella Reddy, Y. C. Janardhan Goyal, Nishant Kesavan, Muralidharan Colomer, Lluc Berk, Michael Kim, Jee Hyun Mol Psychiatry Expert Review Bipolar disorder’s core feature is the pathological disturbances in mood, often accompanied by disrupted thinking and behavior. Its complex and heterogeneous etiology implies that a range of inherited and environmental factors are involved. This heterogeneity and poorly understood neurobiology pose significant challenges to existing drug development paradigms, resulting in scarce treatment options, especially for bipolar depression. Therefore, novel approaches are needed to discover new treatment options. In this review, we first highlight the main molecular mechanisms known to be associated with bipolar depression–mitochondrial dysfunction, inflammation and oxidative stress. We then examine the available literature for the effects of trimetazidine in said alterations. Trimetazidine was identified without a priori hypothesis using a gene-expression signature for the effects of a combination of drugs used to treat bipolar disorder and screening a library of off-patent drugs in cultured human neuronal-like cells. Trimetazidine is used to treat angina pectoris for its cytoprotective and metabolic effects (improved glucose utilization for energy production). The preclinical and clinical literature strongly support trimetazidine’s potential to treat bipolar depression, having anti-inflammatory and antioxidant properties while normalizing mitochondrial function only when it is compromised. Further, trimetazidine’s demonstrated safety and tolerability provide a strong rationale for clinical trials to test its efficacy to treat bipolar depression that could fast-track its repurposing to address such an unmet need as bipolar depression. Nature Publishing Group UK 2023-06-29 2023 /pmc/articles/PMC10618096/ /pubmed/37386057 http://dx.doi.org/10.1038/s41380-023-02134-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Expert Review Khanra, Sourav Reddy, Preethi Giménez-Palomo, Anna Park, Chun Hui J. Panizzutti, Bruna McCallum, Madeleine Arumugham, Shyam Sundar Umesh, Shreekantiah Debnath, Monojit Das, Basudeb Venkatasubramanian, Ganesan Ashton, Melanie Turner, Alyna Dean, Olivia M. Walder, Ken Vieta, Eduard Yatham, Lakshmi N. Pacchiarotti, Isabella Reddy, Y. C. Janardhan Goyal, Nishant Kesavan, Muralidharan Colomer, Lluc Berk, Michael Kim, Jee Hyun Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine |
title | Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine |
title_full | Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine |
title_fullStr | Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine |
title_full_unstemmed | Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine |
title_short | Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine |
title_sort | metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine |
topic | Expert Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618096/ https://www.ncbi.nlm.nih.gov/pubmed/37386057 http://dx.doi.org/10.1038/s41380-023-02134-8 |
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