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Front Physiol. 2018 Mar 12;9:199. doi: 10.3389/fphys.2018.00199. eCollection 2018.

Reciprocal Interactions of Mitochondria and the Neuroimmunoendocrine System in Neurodegenerative Disorders: An Important Role for Melatonin Regulation.

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Department of Gynecology and Reproductology, Ott Institute of Obstetrics, Saint Petersburg, Russia.
Department of Cell Biology and Pathology, Saint-Petersburg Institute of Bioregulation and Gerontology, Saint Petersburg, Russia.
Department of Physiology and Department of Pathology, Saint Petersburg State University, Saint Petersburg, Russia.
CRC Scotland and London Clinical Research, London, United Kingdom.
Cell Reprogramming Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
Division of Internal Medicine and Chronobiology Unit, Department of Medical Sciences, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
Peter the Great Saint Petersburg Polytechnic University, Saint Petersburg, Russia.


Structural and functional alterations of mitochondria are intimately linked to a wide array of medical conditions. Many factors are involved in the regulation of mitochondrial function, including cytokines, chaperones, chemokines, neurosteroids, and ubiquitins. The role of diffusely located cells of the neuroendocrine system, including biogenic amines and peptide hormones, in the management of mitochondrial function, as well as the role of altered mitochondrial function in the regulation of these cells and system, is an area of intense investigation. The current article looks at the interactions among the cells of the neuronal-glia, immune and endocrine systems, namely the diffuse neuroimmunoendocrine system (DNIES), and how DNIES interacts with mitochondrial function. Whilst changes in DNIES can impact on mitochondrial function, local, and systemic alterations in mitochondrial function can alter the component systems of DNIES and their interactions. This has etiological, course, and treatment implications for a wide range of medical conditions, including neurodegenerative disorders. Available data on the role of melatonin in these interactions, at cellular and system levels, are reviewed, with directions for future research indicated.


DNIES; melatonin; mitochondrion; neurodegeneration; neuroimmunoendocrine

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