New Delhi, 2 January (H.S.): Scientists have proved that nano-formulation of melatonin, a hormone produced by the brain in response to darkness, has shown superior antioxidant and neuroprotective properties and could be a potential therapeutic solution for Parkinson's disease (PD).

Parkinson's disease (PD) is one of the most common neurological disorders caused by the death of dopamine-secreting neurons in the brain due to the aggregation of synuclein protein inside it. Available drugs can only alleviate the symptoms but cannot cure the disease and this underlines the need to develop better therapeutic solutions for the disease.

Studies over the last decade have shown the implications of PD-related genes in controlling a quality control mechanism called mitophagy, which identifies and removes dysfunctional mitochondria and reduces oxidative stress.

Among the many antioxidants, melatonin is a neurohormone secreted by the pineal gland, an endocrine gland in the brain, which regulates the sleep-wake cycle and is used to treat insomnia. It may be a potential inducer of mitophagy to alleviate PD. The molecular pathways that melatonin follows as a PD antagonist are poorly elucidated despite being a safe and potential neurotherapeutic drug with certain limitations such as low bioavailability, premature oxidation, brain distribution, etc.

A group of researchers from the Institute of Nano Science and Technology (INST) Mohali (Punjab), an autonomous institute of the Department of Science and Technology (DST), used human serum albumin nano-formulation to deliver the drug to the brain and studied the molecular mechanisms behind melatonin-mediated oxidative stress regulation.

Using biocompatible protein (HSA) nanocarriers to deliver melatonin to the brain, Dr. Surjeet Karmakar and his team have proven that nano-melatonin resulted in sustained release of melatonin and improved bioavailability. They found that nano-melatonin exhibited improved antioxidant and neuroprotective properties. It not only improved mitophagy to remove unhealthy mitochondria but also improved mitochondrial biogenesis to combat pesticide (rotenone) induced toxicity in an in vitro PD model. This improvement is attributed to the sustained release of melatonin and targeted delivery to the brain, resulting in enhanced therapeutic efficacy compared to bare melatonin. The enhanced antioxidant effect is a result of mitophagy induction through upregulation of an important epigenetic regulator called BMI1, which controls gene expression.Reduction in oxidative stress contributes to the reduction of symptoms of Parkinson's disease. Their findings, published in the journal ACS Applied Materials and Interfaces, shed much better light on the in vitro and in vivo neuroprotective effects of nano-melatonin as well as the molecular/cellular dynamics influenced by it to regulate mitophagy. The experiments showed that the nano-formulation of melatonin also protected TH-positive neurons against rotenone-mediated toxicity in the brain of mice. Additionally, the study revealed for the first time that BMI1, a member of the Polycomb Repressive Complex One, the most essential family of proteins responsible for epigenetic regulation, was over-expressed after nano-formulation treatment. This over-expression induced mitophagy may help protect neurons from degeneration. The study unravels the molecular mechanism behind melatonin-mediated mitophagy regulation.

Increased mitophagy was important for reducing oxidative stress in Parkinson's disease model. Melatonin-mediated BMI1 regulation and the subsequent role in inducing mitophagy to prevent oxidative stress may pave the way to establish melatonin as a therapeutic candidate for Parkinson's disease. It can also be used to treat other diseases where disordered mitophagy is important for disease outcomes. With continued exploration it can be established as a safe drug to improve the lives of patients.

Hindusthan Samachar / Jun Sarkar