Melatonin and Melatonergic Influence on Neuronal Transcription Factors: Implications for the Development of Novel Therapies for Neurodegenerative Disorders

Abstract

: Melatonin is a multifunctional signalling molecule that is secreted by the mammalian pineal gland, and also found in a number of organisms including plants and bacteria. Research has continued to uncover an ever-increasing number of processes in which melatonin is known to play crucial roles in mammals. Amongst these functions is its contribution to cell multiplication, differentiation and survival in the brain. Experimental studies show that melatonin can achieve these functions by influencing transcription factors which control neuronal and glial gene expression. Since neuronal survival and differentiation are processes that are important determinants of the pathogenesis, course and outcome of neurodegenerative disorders; the known and potential influences of melatonin on neuronal and glial transcription factors are worthy of constant examination. In this review, we examine relevant scientific literature on the role of melatonin in preventing, or altering the course and outcome of neurodegenerative disorders, by focusing on melatonin’s influence on transcription factors. We also highlight a number of transcription factors whose functions can be influenced by melatonin in neurodegenerative disease models. Finally, we discuss the therapeutic implications of melatonin’s influences, and highlight the potential limitations to its applications.

Increased Oxidative Stress Markers in Acute Ischemic Stroke Patients Treated with Thrombolytics

“…This could suggest that patients treated with thrombolysis have impaired urinary excretion of the metabolite and low antioxidant protection. Similarly, a reduced level of serum melatonin and its metabolites in the urine of patients with stroke has been confirmed by other researchers [ 23 , 24 , 25 , 26 , 27 ]. In our study, an increase in the concentration of the melatonin metabolite was observed within the first 24 h compared to its level before <4.5 h in patients treated with thrombolytic therapy.…”

Intestinal microbiota and melatonin in the treatment of secondary injury and complications after spinal cord injury

“…Melatonin is known to have a variety of biological functions, including circadian rhythm regulation, anti-inflammatory, free radical scavenging, edema reduction, suppression of the hypothalamic-pituitary endocrine axis, suppression of cancer, stimulation of mitochondrial biogenesis, immunomodulation, blood pressure regulation and the epigenetic regulation, and has therapeutic effects on a variety of secondary injuries after SCI ( Giannoulia-Karantana et al, 2006 ; de Faria Poloni et al, 2011 ; Mazzoccoli et al, 2011 ; Xu L.X. et al, 2017 ; Chang et al, 2018 ; Onaolapo et al, 2020 ; Cho et al, 2021 ; Vasey et al, 2021 ). Melatonin can also regulate the intestinal biological clock and the types of intestinal microbiota, improve the metabolic disorder caused by intestinal microbiota imbalance after SCI, and indirectly play a role in the recovery of function and the treatment of complications ( Paulose et al, 2016 ).…”

Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action

“…The chief function of melatonin is to transmit information on the daily light and darkness cycle (Claustrat et al 2005 ) and it plays a key role in the regulation of the sleep-awakeness cycle, puberty development, seasonal adaptation and memory formation (Giannoulia-Karantana et al 2007 ; Skarlis and Anagnostouli 2020 ). Furthermore, melatonin is known to be a multifunctional molecule (Onaolapo et al 2019 ), and has been seen to have an anti-oxidant, anti-inflammatory (Escribano et al 2014 ) and anti-apoptotic capacity, as well as acting in immune responses and mitochondrial homeostasis (Carrascal et al 2018 ) contributing to the multiple cell differentiation and survival in the brain (Onaolapo et al 2019 ).…”