Pineal Melatonin Functions: Possible Relevance to Parkinson's Disease

Abstract

Barbeau hypothesized that Parkinson's disease is associated with hypothalamic deficiency of the specialized neuroendocrine cell system (A.P.U.D.) and that the degeneration of brainstem monoaminergic neurons is secondary to progressive functional loss of this cell system in the disease. The pineal gland meets criteria of the A.P.U.D. cell system and it is possible that dysfunction of the pineal gland may be associated with the pathophysiology and clinical manifestations of Parkinson's disease. Since the role of pineal melatonin in humans remains enigamatic, it is currently unclear which of the symptoms of Parkinson's disease may be associated with deregulation of the secretory activity of pineal melatonin. This review summarizes evidence linking possible alterations of pineal melatonin functions with the clinical manifestations of Parkinson's disease.

Circadian secretion pattern of melatonin in Parkinson's disease

“…Melatonin administration increased brain 5-HT concentrations (Cotzias etal., 1971), so that a possible modulation of nigrostriatal dopaminergic activity in Parkinson's disease was suggested in an indirect way; serotoninergic neurons originating from the raphe nuclei and innervating the striatum may suppress the release of dopamine. Speculation that the occurence of on-off-phenomena in Parkinson's disease is related to fluctuation of the serum melatonin level (Sandyk, 1990) is not supported by our data.…”

Endogenous regulator of brain aging and neurodegeneration-One target multiple therapeutic interventions

“…In humans melatonin levels decrease with advancing age and interestingly its levels are reduced in AD [1,2] and HT [3]. Whereas in PD; reduced concentration of circulating melatonin has been reported in PD patients [4] with different variations [5]. Changes in melatonin levels have also been observed in multiple sclerosis and cerebral ischemia [6] along with altered secretion and levels in cancer patients (for review; [7].…”

Melatonin as a Neuroprotective Agent in the Rodent Models of Parkinson’s Disease: Is it All Set to Irrefutable Clinical Translation?

“…Melatonin reduces neuroinflammation, oxidative stress, and cell adhesion, and restores mitochondrial function [4,8] and also acts as an important component of the brain's anti-oxidant defense system against catecholamine auto-oxidation and protects against the consequent dopaminergic neurodegeneration [99]. This idea gained momentum from the fact that pineal gland meets the criteria of the neuroendocrine system, and dysfunction of the pineal gland may be associated with the pathophysiology and clinical manifestations of PD [100]. Although initially it was considered that melatonin offers neuroprotection by restoring its level or by improving the restoration of the expression of TH by reducing its oxidation [7], several theories have been documented till date.…”