Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases
Multiple lines of evidence have shown that lactate-mediated pH alterations in the brains of patients with neuropsychiatric diseases such as schizophrenia (SCZ), Alzheimer’s disease (AD) and autism may be attributed to mitochondrial dysfunction and changes in energy metabolism. While neuronal activit...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/2/457 |
| _version_ | 1797298860276580352 |
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| author | Shabnam Nohesara Hamid Mostafavi Abdolmaleky Sam Thiagalingam |
| author_facet | Shabnam Nohesara Hamid Mostafavi Abdolmaleky Sam Thiagalingam |
| author_sort | Shabnam Nohesara |
| collection | DOAJ |
| description | Multiple lines of evidence have shown that lactate-mediated pH alterations in the brains of patients with neuropsychiatric diseases such as schizophrenia (SCZ), Alzheimer’s disease (AD) and autism may be attributed to mitochondrial dysfunction and changes in energy metabolism. While neuronal activity is associated with reduction in brain pH, astrocytes are responsible for rebalancing the pH to maintain the equilibrium. As lactate level is the main determinant of brain pH, neuronal activities are impacted by pH changes due to the binding of protons (H<sup>+</sup>) to various types of proteins, altering their structure and function in the neuronal and non-neuronal cells of the brain. Lactate and pH could affect diverse types of epigenetic modifications, including histone lactylation, which is linked to histone acetylation and DNA methylation. In this review, we discuss the importance of pH homeostasis in normal brain function, the role of lactate as an essential epigenetic regulatory molecule and its contributions to brain pH abnormalities in neuropsychiatric diseases, and shed light on lactate-based and pH-modulating therapies in neuropsychiatric diseases by targeting epigenetic modifications. In conclusion, we attempt to highlight the potentials and challenges of translating lactate-pH-modulating therapies to clinics for the treatment of neuropsychiatric diseases. |
| first_indexed | 2024-03-07T22:41:09Z |
| format | Article |
| id | doaj.art-f22abff0bc1f4467b94f19b999fee350 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-07T22:41:09Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-f22abff0bc1f4467b94f19b999fee3502024-02-23T15:08:54ZengMDPI AGBiomedicines2227-90592024-02-0112245710.3390/biomedicines12020457Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental DiseasesShabnam Nohesara0Hamid Mostafavi Abdolmaleky1Sam Thiagalingam2Department of Medicine (Biomedical Genetics), Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USADepartment of Medicine (Biomedical Genetics), Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USADepartment of Medicine (Biomedical Genetics), Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USAMultiple lines of evidence have shown that lactate-mediated pH alterations in the brains of patients with neuropsychiatric diseases such as schizophrenia (SCZ), Alzheimer’s disease (AD) and autism may be attributed to mitochondrial dysfunction and changes in energy metabolism. While neuronal activity is associated with reduction in brain pH, astrocytes are responsible for rebalancing the pH to maintain the equilibrium. As lactate level is the main determinant of brain pH, neuronal activities are impacted by pH changes due to the binding of protons (H<sup>+</sup>) to various types of proteins, altering their structure and function in the neuronal and non-neuronal cells of the brain. Lactate and pH could affect diverse types of epigenetic modifications, including histone lactylation, which is linked to histone acetylation and DNA methylation. In this review, we discuss the importance of pH homeostasis in normal brain function, the role of lactate as an essential epigenetic regulatory molecule and its contributions to brain pH abnormalities in neuropsychiatric diseases, and shed light on lactate-based and pH-modulating therapies in neuropsychiatric diseases by targeting epigenetic modifications. In conclusion, we attempt to highlight the potentials and challenges of translating lactate-pH-modulating therapies to clinics for the treatment of neuropsychiatric diseases.https://www.mdpi.com/2227-9059/12/2/457neuropsychiatric diseasespHlactatelactylationDNA methylationhistone acetylation |
| spellingShingle | Shabnam Nohesara Hamid Mostafavi Abdolmaleky Sam Thiagalingam Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases Biomedicines neuropsychiatric diseases pH lactate lactylation DNA methylation histone acetylation |
| title | Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases |
| title_full | Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases |
| title_fullStr | Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases |
| title_full_unstemmed | Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases |
| title_short | Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases |
| title_sort | potential for new therapeutic approaches by targeting lactate and ph mediated epigenetic dysregulation in major mental diseases |
| topic | neuropsychiatric diseases pH lactate lactylation DNA methylation histone acetylation |
| url | https://www.mdpi.com/2227-9059/12/2/457 |
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