The Role of Melatonin in Multiple Sclerosis, Huntington's Disease and Cerebral Ischemia

Abstract

Melatonin is produced and released by the pineal gland in a circadian rhythm. This neurohormone has proven to be an antioxidant and anti-inflammatory molecule able to reduce or mitigate cell damage associated with oxidative stress and inflammation, and this phenomenon underlies neurodegenerative disorders. These facts have drawn attention to this indole, triggering interest in evaluating its changes and in its relationship to the processes indicated, and analyzing its role in the mechanisms involved at the onset and development of neurodegenerative diseases, as well as its therapeutic potential. Multiple sclerosis, the most common cause of non-traumatic disability in young adults, is a chronic neuroinflammatory disease, characterized by demyelination, inflammation, and neuronal and oxidative damage. In its early diagnosis, it often requires a differential screening with other neurodegenerative diseases with similar symptoms, such as Huntington's disease, an autosomal dominant disorder. The onset of both diseases occurs in the second or third decade of life. On the other hand, cerebral ischemia is a major cause of human disability all over the world. Although a cerebral stroke can occur as the result of different damaging insults, severe ischemia produces the death of neuronal cells within minutes. Changes in melatonin levels have been observed in these processes (Huntington's disease, multiple sclerosis and cerebral ischemia) as part of their pathogenic features. This review aims to update and discuss the role played by melatonin during neurodegenerative processes, specifically in multiple sclerosis, Huntington's disease, and cerebral ischemia, and its possible therapeutic use. We also provide readers with an update on the many neuroprotective mechanisms exerted by this neurohormone in the Central Nervous System.

Age-Related Changes in the Melatonin and Thymulin Biorhythms as Risk Factors for Human Neurodegenerative Diseases

“…In the opinion of Escribano and co-worker [38], decrease of melatonin level in this pathology is a part of its pathogenic features. Thus, in cerebral ischemia melatonin reveals antioxidant, antiapoptotic and anti-inflammatory properties [39].…”

Update on melatonin receptors: IUPHAR Review 20

“…Additional evidence supports the emerging concept of MT receptor dysfunction as a permissive condition favouring the development and/or progression of neurodegenerative diseases. The neuroprotective effect of endogenous and exogenous melatonin has been demonstrated in different systems (see Escribano et al, ). In a neuroinflammatory model induced by LPS administration, cerebellar neuronal death was observed only in animals pretreated with luzindole (Pinato et al, ).…”

Melatonin protects the retina from experimental nonexudative age‐related macular degeneration in mice

“…Moreover, SCGx induces an increase in several markers of oxidative stress, and a decrease both in the central temporal (without any nasal alterations) RPE mitochondria mass and endogenous antioxidant system enzymes . Melatonin is a molecule with proven antioxidant and anti‐inflammatory activities, which reduces oxidative stress and inflammatory cell damage often underling neurodegenerative disorders (reviewed in). Evidence strongly supports that melatonin and its metabolites act both as direct and indirect antioxidants by free radicals scavengers, antioxidant enzymes stimulators and other antioxidants activities enhancers .…”