In animals, melatonin, N-acetyl-5-methoxy tryptamine, is a hormone produced and secreted by the pineal gland. It is involved in the synchronization of the circadian rhythms of e.g. sleep and blood pressure.
Melatonin works in two ways: through activation of melatonin receptors, and as an antioxidant that can easily cross cell membranes and the blood–brain barrier.
As an antioxidant, melatonin is a direct scavenger of radical oxygen and nitrogen species, and its metabolites are also scavengers. Moreover, it has amphiphilic properties. Melatonin seems to be a more effective protector against mitochondrial oxidative stress than synthetic antioxidants. A particular function of melatonin is to protect nuclear and mitochodrial DNA. Melatonin also interacts with the immune system, having anti-inflammatory effects.
Effects on ALS
In ALS, the most promising effects of melatonin are those of blocking apoptotic pathways and reducing oxidative damage caused by free radicals by scavenging. The mechanisms of melatonin antiapoptotic effects are not completely clear, although the mitochondria have been identified as its target. ,
Melatonin is a molecule with numerous properties applicable to the treatment of neurological diseases. Among these properties are the following: potent scavenger of oxygen and nitrogen reactive species, anti-inflammatory features, immuno-enhancing nature, and modulation of circadian rhythmicity. 
Can cause some side effects including headache, short-term feelings of depression, daytime sleepiness, dizziness, stomach cramps, and irritability. Do not drive or use machinery for four to five hours after taking melatonin. (Source: WebMD) Can cause reduced blood flow and hypothermia (in the elderly). In auto-immune disorders, it is unclear whether melatonin may either ameliorate or exacerbate symptoms due to immunomodulation. Can lower FSH levels, and effects on human reproduction remain unclear. Anticoagulants and other substances are known to interact with melatonin. (Source: Wikipedia)
- de Paula et al.: An Overview of Potential Targets for Treating Amyotrophic Lateral Sclerosis and Huntington's Disease. Biomed Res Int 2015;2015:198612. PMID: 26295035. DOI. Neurodegenerative diseases affect millions of people worldwide. Progressive damage or loss of neurons, neurodegeneration, has severe consequences on the mental and physical health of a patient. Despite all efforts by scientific community, there is currently no cure or manner to slow degeneration progression. We review some treatments that attempt to prevent the progress of some of major neurodegenerative diseases: Amyotrophic Lateral Sclerosis and Huntington's disease.
- Weishaupt et al.: Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J. Pineal Res. 2006;41:313-23. PMID: 17014688. DOI. Amyotrophic lateral sclerosis (ALS) is the collective term for a fatal motoneuron disease of different etiologies, with oxidative stress as a common molecular denominator of disease progression. Melatonin is an amphiphilic molecule with a unique spectrum of antioxidative effects not conveyed by classical antioxidants. In preparation of a possible future clinical trial, we explored the potential of melatonin as neuroprotective compound and antioxidant in: (1) cultured motoneuronal cells (NSC-34), (2) a genetic mouse model of ALS (SOD1(G93A)-transgenic mice), and (3) a group of 31 patients with sporadic ALS. We found that melatonin attenuates glutamate-induced cell death of cultured motoneurons. In SOD1(G93A)-transgenic mice, high-dose oral melatonin delayed disease progression and extended survival. In a clinical safety study, chronic high-dose (300 mg/day) rectal melatonin was well tolerated during an observation period of up to 2 yr. Importantly, circulating serum protein carbonyls, which provide a surrogate marker for oxidative stress, were elevated in ALS patients, but were normalized to control values by melatonin treatment. This combination of preclinical effectiveness and proven safety in humans suggests that high-dose melatonin is suitable for clinical trials aimed at neuroprotection through antioxidation in ALS.
- Sánchez-Barceló et al.: Clinical Uses of Melatonin in Neurological Diseases and Mental and Behavioural Disorders. Curr. Med. Chem. 2017;. PMID: 28721826. DOI. Melatonin is a molecule with numerous properties applicable to the treatment of neurological diseases. Among these properties are the following: potent scavenger of oxygen and nitrogen reactive species, anti-inflammatory features, immuno-enhancing nature, and modulation of circadian rhythmicity. Furthermore, low concentrations of melatonin are usually found in patients with neurological diseases and mental disorders. The positive results obtained in experimental models of diverse pathologies, including diseases of the nervous system (e.g., Alzheimer´s disease, Parkinson´s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington´s disease, epilepsy, headaches, etc.) as well as mental and behavioural disordes (e.g., autism spectrum disorders, attention-deficit hyperactivity disorders, etc.), have served as a basis for the design of clinical trials to study melatonin's possible usefulness in human pathology, although the satisfactory results obtained from the laboratory "bench" are not always applicable to the patient's "bedside". OBJECTIVE: In this article, we review those papers describing the results of the administration of melatonin to humans for various therapeutic purposes in the field of neuropathology. CONCLUSION: Clinical trials with strong methodologies and appropriate doses of melatonin are necessary to support or reject the usefulness of melatonin in neurological diseases.