Role of immune-pineal axis in neurodegenerative diseases, unraveling novel hybrid dark hormone therapies

Abstract

The anti-oxidant effects of melatonin and the immune-pineal axis are well established. However, how they play a role in the pathogenesis of neurodegenerative diseases is not well elucidated. A better understanding of this neuro-immuno-endocrinological link can help in the development of novel therapies with higher efficacy to alleviate symptomatology, slow disease progression and improve the quality of life. Recent studies have shown that the immune-pineal axis acts as an immunological buffer, neurohormonal switch and it also intricately links the pathogenesis of neurodegenerative diseases (like Multiple sclerosis, Alzheimer's disease, Parkinson's disease) and inflammation at a molecular level. Furthermore, alteration in circadian melatonin production is seen in neurodegenerative diseases. This review will summarise the mechanics by which the immune-pineal axis and neuro-immuno-endocrinological disturbances affect the pathogenesis and progression of neurodegenerative diseases. It will also explore, how this understanding will help in the development of novel hybrid melatonin hormone therapies for the treatment of neurodegenerative diseases.

Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances

“…The main objective of the study was to investigate as to whether an increase in TNF in ASD is associated with daily melatonin rhythm, given the role of TNF in regulating the immune-pineal axis in other medical conditions. 24,42,43 TNF is a highly investigated cytokine, with a number of important physiological and pathophysiological roles, including in brain development, cell survival/apoptosis, neurogenesis, and cell differentiation. 44 Consequently, TNF can regulate key processes associated with ASD pathophysiology, including cognition.…”

“…Although there was a substantial variance between subjects, the within‐subject daily aMT6s rhythm was highly consistent. The main objective of the study was to investigate as to whether an increase in TNF in ASD is associated with daily melatonin rhythm, given the role of TNF in regulating the immune‐pineal axis in other medical conditions 24,42,43 …”

Effect of Melatonin on Serum Levels of INF-1β and Vitamin B12 in Patients With Multiple Sclerosis: A Randomized Controlled Trial

“…Therefore, melatonin may be used as an auxiliary, safe and affordable medication with minimal side effects and low toxicity risk to effectively manage the MS symptoms. Several studies have also shown that melatonin has anti-inflammatory properties and leads to the alleviation of fatigue states in MS patients [40][41][42][43]. Also, Jamshidi-Fard et al [42] and Wurtman [43] have shown that melatonin is effective in treating the visual impairment in MS patients.…”

Melatonin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-related Diseases

“…However, further investigation regarding the role of melatonin in hematopoiesis is required. Furthermore, over the course of the inflammatory response, TNF inhibits nocturnal pineal synthesis and induces the synthesis of melatonin by macrophages and other immunocompetent cells [ 25 , 28 ]. In mammals, nuclear translocation of NF-κB blocks noradrenaline-induced melatonin synthesis in pinealocytes, which induces melatonin synthesis in macrophages [ 29 ].…”