Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders
Although previously restricted to a limited number of medical conditions, there is a growing appreciation that ‘autoimmune’ (or immune-mediated) processes are important aspects of a wide array of diverse medical conditions, including cancers, neurodegenerative diseases and psychiatric disorders. All...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/9/1237 |
| _version_ | 1827743227240775680 |
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| author | George Anderson Abbas F. Almulla Russel J. Reiter Michael Maes |
| author_facet | George Anderson Abbas F. Almulla Russel J. Reiter Michael Maes |
| author_sort | George Anderson |
| collection | DOAJ |
| description | Although previously restricted to a limited number of medical conditions, there is a growing appreciation that ‘autoimmune’ (or immune-mediated) processes are important aspects of a wide array of diverse medical conditions, including cancers, neurodegenerative diseases and psychiatric disorders. All of these classes of medical conditions are associated with alterations in mitochondrial function across an array of diverse cell types. Accumulating data indicate the presence of the mitochondrial melatonergic pathway in possibly all body cells, with important consequences for pathways crucial in driving CD8<sup>+</sup> T cell and B-cell ‘autoimmune’-linked processes. Melatonin suppression coupled with the upregulation of oxidative stress suppress PTEN-induced kinase 1 (PINK1)/parkin-driven mitophagy, raising the levels of the major histocompatibility complex (MHC)-1, which underpins the chemoattraction of CD8<sup>+</sup> T cells and the activation of antibody-producing B-cells. Many factors and processes closely associated with autoimmunity, including gut microbiome/permeability, circadian rhythms, aging, the aryl hydrocarbon receptor, brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) all interact with the mitochondrial melatonergic pathway. A number of future research directions and novel treatment implications are indicated for this wide collection of poorly conceptualized and treated medical presentations. It is proposed that the etiology of many ‘autoimmune’/‘immune-mediated’ disorders should be conceptualized as significantly determined by mitochondrial dysregulation, with alterations in the mitochondrial melatonergic pathway being an important aspect of these pathoetiologies. |
| first_indexed | 2024-03-11T04:22:33Z |
| format | Article |
| id | doaj.art-bf6e8624a33f41da809b7180ca6cfdd2 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T04:22:33Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-bf6e8624a33f41da809b7180ca6cfdd22023-11-17T22:43:11ZengMDPI AGCells2073-44092023-04-01129123710.3390/cells12091237Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune DisordersGeorge Anderson0Abbas F. Almulla1Russel J. Reiter2Michael Maes3CRC Scotland & London, Eccleston Square, London SW1V 1PG, UKDepartment of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Cell Systems and Anatomy, UT Health Long School of Medicine, San Antonio, TX 78229, USADepartment of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandAlthough previously restricted to a limited number of medical conditions, there is a growing appreciation that ‘autoimmune’ (or immune-mediated) processes are important aspects of a wide array of diverse medical conditions, including cancers, neurodegenerative diseases and psychiatric disorders. All of these classes of medical conditions are associated with alterations in mitochondrial function across an array of diverse cell types. Accumulating data indicate the presence of the mitochondrial melatonergic pathway in possibly all body cells, with important consequences for pathways crucial in driving CD8<sup>+</sup> T cell and B-cell ‘autoimmune’-linked processes. Melatonin suppression coupled with the upregulation of oxidative stress suppress PTEN-induced kinase 1 (PINK1)/parkin-driven mitophagy, raising the levels of the major histocompatibility complex (MHC)-1, which underpins the chemoattraction of CD8<sup>+</sup> T cells and the activation of antibody-producing B-cells. Many factors and processes closely associated with autoimmunity, including gut microbiome/permeability, circadian rhythms, aging, the aryl hydrocarbon receptor, brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) all interact with the mitochondrial melatonergic pathway. A number of future research directions and novel treatment implications are indicated for this wide collection of poorly conceptualized and treated medical presentations. It is proposed that the etiology of many ‘autoimmune’/‘immune-mediated’ disorders should be conceptualized as significantly determined by mitochondrial dysregulation, with alterations in the mitochondrial melatonergic pathway being an important aspect of these pathoetiologies.https://www.mdpi.com/2073-4409/12/9/1237autoimmunitymitochondriamelatoninN-acetylserotoninaryl hydrocarbon receptorTrkB |
| spellingShingle | George Anderson Abbas F. Almulla Russel J. Reiter Michael Maes Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders Cells autoimmunity mitochondria melatonin N-acetylserotonin aryl hydrocarbon receptor TrkB |
| title | Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders |
| title_full | Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders |
| title_fullStr | Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders |
| title_full_unstemmed | Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders |
| title_short | Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders |
| title_sort | redefining autoimmune disorders pathoetiology implications for mood and psychotic disorders association with neurodegenerative and classical autoimmune disorders |
| topic | autoimmunity mitochondria melatonin N-acetylserotonin aryl hydrocarbon receptor TrkB |
| url | https://www.mdpi.com/2073-4409/12/9/1237 |
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