It seems that the deficiency of melatonin may be one of the factors increasing the risk of neurodegenerative disease development. Melatonin may be one of the main antioxidant factors present in the nervous system, so if it is in decreased levels there is not enough protection for the nervous tissue.

Since Melatonin is produced during the dark phase/night of most vertebrates disturbances in the rhythmic production indicates changes/defects in the circadian clock system. Since its known that bad sleep and erratic activity cycles in humans are early indicators of neurodegenerative diseases, melatonin serves as an indicator for such changes. On the other hand there are people who do not produce pineal melatonin due to excised tumors in the pineal region and I have never heard of higher incidence of neurodegenerative diseases in such patients. It may thus be helpful to investigate this small group (those without a functional pineal gland) to evaluate a potential protective action of melatonin for neurodegenerative disease. 

As Erik said above "On the other hand there are people who do not produce pineal melatonin due to excised tumors in the pineal region and I have never heard of higher incidence of neurodegenerative diseases in such patients.", which means that the decrease of melatonin amount in patients suffering neurodegenrative disorders is not a direct cause but a result of the degeneration. However, the neuroprotective role of melatonin through its antioxidative effect was showed a long time ago by many researchers! My question is: is there anyone who showed (by experimentation) that the advancement of degenration (in Alzheimer or Parkinson disease) is directly related to melatonin secretion decrease in CNS and vice versa?

Dear Mohamed

Melatonin concentration declines in either MS patients or animal models of EAE, as studied by others and our setudy. Then, we found that melatonin stimulates oligodendrogensis in clutured neural stem cell. Please have a look to following references

https://www.ncbi.nlm.nih.gov/pubmed/27696474

https://www.ncbi.nlm.nih.gov/pubmed/27987059

Beside pinealectomized patients who do not seem to experience more neurodegenerative diseases than the general population (at least this has never been described in the literature to the best of my knowledge) another argument is that the use of beta-blockers (that block melatonin secretion) do not seem either to increase neurodegeneration.

The pineal hormone melatonin is involved in physiological transduction of temporal information from the light dark cycle to circadian and seasonal behavioural rhythms, as well as possessing neuroprotective properties. Melatonin and its receptors MT1 and MT2, which belong to the family of G protein-coupled receptors, are impaired in Alzheimer's disease (AD) with severe consequences to neuropathology and clinical symptoms. Please see attached paper particularly related with the altered expression of MT2 receptors in AD.

Changing the generation of circadian

Melatonin is involved in the development of degenerative changes in the brain that occur

already in normal aging, but increase with age-associated

diseases, especially Alzgeimer disease and cardiovascular disease.At

Experimental studies have shown neuroprotective properties of melatonin

in case of brain, s infarct that are associated with a reduction of oxidative damage,

the regulation of the level of calcium ions, anti-apoptotic activity, protection of glial

cells and anti-inflammatory effect.

sleep disturpence  for example shift work greatly influence the normal melatonin secretions and ther for it has great impacts on neurons degeneration

The daily sleep-wake cycle is influenced by 2 factors: process C (circadian), an endogenous “clock” that drives the rhythm of the sleep-wake cycle; and process S (sleep), a homeostatic “sleep propensity” that determines the recent amount of sleep and wakefulness accumulated. The SCN interacts with both processes, and it is where the main component of process C is located. Excitatory signals from the SCN and subsequent melatonin suppression are thought to promote wakefulness during the day in response to light and the suppression of melatonin inhibition of the SCN. This inhibition is released in the dark phase and leads to melatonin synthesis/release with consequent sleep promotion.

The sleep-wake cycle is only one of many circadian rhythms. Left without stimulus, the circadian period of sleep/wake is around 24.2 hours, but this can vary from 23.8 to 27.1 hours. This period is inherited and is closely related to intrinsic circadian preference for nighttime (long period) or daytime (short period), which can be determined by measuring the timing of maximal secretion of melatonin and subsequent related core body temperature (CBT). Maximum sleepiness occurs when CBT is at its lowest and melatonin levels are at their highest.

Many exogenous and endogenous factors (called zeitgebers) can shift a circadian rhythm. The sleep-wake cycle only becomes entrained to the 24-hour solar day by these factors, and by far the most powerful is ocular light exposure. The use of exogenous melatonin is one of the major non-light factors that can entrain the circadian rhythm, but results in clinical samples have been mixed.3 This is not surprising because there can be great individual variability in endogenous melatonin production. Light, medication, and behavior can also change melatonin levels. The pharmacokinetics and pharmacodynamics of exogenous melatonin (high first-pass metabolism, short half-life, and weak MT1/MT2 receptor binding) may also lead to the inconsistent effects in many clinical spheres as well.

Melatonin appears to have 2 probable interacting effects on the sleep-wake cycle. First, it entrains and shifts the circadian rhythm (process C) in a “chronobiotic” function. Second, it promotes sleep onset and continuity in a “hypnotic” function by increasing the homeostatic drive to sleep (process S). These effects appear to be equal. Clinically, exogenous melatonin given in the morning delays the phase of circadian rhythm and subsequent evening sleepiness. Melatonin given in the evening can advance both of these phases.

From the available literature and the answers above I conclude that no one really proved that melatonin is directly linked to neurodegeneration and this despite its indirect role in the potentiation of such disorders!