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Has Indian Scientists Found a Breakthrough Solution for Parkinson’s Disease?

A team of Indian researchers from the Institute of Nano Science and Technology (INST), Mohali, led by Dr. Surajit Karmakar, has developed a nano-formulation of melatonin that could revolutionize the treatment of Parkinson’s disease (PD).

• By Pooja Chaturvedi Sah
• New Delhi
• Jan 03, 2025

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A team of Indian researchers from the Institute of Nano Science and Technology (INST), Mohali, led by Dr. Surajit Karmakar, has developed a nano-formulation of melatonin that could revolutionize the treatment of Parkinson’s disease (PD). This innovative approach enhances the neuroprotective and antioxidative properties of melatonin, a hormone known for regulating sleep, by addressing its limitations in bioavailability and brain delivery. 

The research, funded by the Department of Science and Technology (DST), has been published in the journal ACS Applied Materials & Interfaces and holds the potential to not only manage PD but also treat other neurodegenerative disorders caused by mitochondrial dysfunction. 

Understanding Parkinson’s Disease 

Parkinson’s disease, a progressive neurological disorder, is one of the most common neurodegenerative diseases worldwide. It primarily affects movement due to the death of dopamine-producing neurons in the brain. This neuronal loss is often triggered by the aggregation of synuclein proteins, leading to oxidative stress and mitochondrial dysfunction. 

Symptoms of Parkinson’s include tremors, rigidity, bradykinesia (slowness of movement), and difficulties with balance. Current therapies, such as levodopa, only alleviate symptoms without addressing the root causes, underscoring the need for advanced therapeutic solutions. 

Melatonin’s Role in Neuroprotection 

Melatonin, a neurohormone produced by the pineal gland, is well known for regulating sleep-wake cycles. However, its antioxidant properties and potential to regulate a cellular process called mitophagy have drawn the attention of researchers. Mitophagy acts as a quality control mechanism in cells, identifying and removing damaged mitochondria to reduce oxidative stress. 

Dysfunctional mitophagy is a hallmark of Parkinson’s disease, contributing to neuronal degeneration. While melatonin shows promise as a mitophagy inducer, its use in therapy has been hindered by challenges such as poor bioavailability, premature oxidation in the body and difficulty in crossing the blood-brain barrier to reach affected brain regions. 

Nano-Melatonin: A Breakthrough Solution 

To overcome these limitations, the team at INST developed a human serum albumin (HSA) nano-formulation of melatonin. The nano-drug enhances melatonin’s delivery to the brain, allowing for sustained release and increased therapeutic efficacy. 

Mechanism of Action 

The nano-melatonin formulation was tested in a Parkinson’s disease model induced by rotenone, a pesticide known to cause mitochondrial toxicity. 

Key findings include: 

1. Enhanced Mitophagy: The nano-formulation improved the removal of damaged mitochondria, reducing oxidative stress and protecting neurons. 

2. Mitochondrial Biogenesis: It also promoted the creation of new, healthy mitochondria, further supporting cellular energy production. 

3. Epigenetic Regulation: The study identified that nano-melatonin upregulated BMI1, a crucial epigenetic regulator in the Polycomb Repressive Complex 1. This protein influences gene expression to enhance mitophagy and protect neurons from degeneration. 

Neuroprotective Benefits 

In both in vitro and in vivo models, nano-melatonin demonstrated superior neuroprotective properties compared to regular melatonin. In particular, the drug: 

• Protected dopamine-producing neurons from degeneration caused by rotenone toxicity. 

• Reduced oxidative stress, a primary driver of neurodegeneration. 

• Improved overall mitochondrial health in neurons. 

Notably, experiments on animal models showed that the nano-formulation protected neurons from rotenone-induced damage, highlighting its therapeutic potential for Parkinson’s disease. 

Implications Beyond Parkinson’s Disease 

The success of nano-melatonin in regulating mitophagy and reducing oxidative stress extends its potential application to other neurodegenerative disorders, including: 

• Alzheimer’s disease: Characterized by mitochondrial dysfunction and oxidative stress. 

• Huntington’s disease: Linked to mitochondrial impairments and cellular toxicity. 

The ability of nano-melatonin to target mitochondrial health and regulate oxidative damage positions it as a versatile therapeutic candidate for various diseases. 

Published Findings and Future Directions 

The findings, published in ACS Applied Materials & Interfaces, represent a significant leap in understanding how melatonin-mediated mitophagy regulation can be harnessed to treat neurodegenerative conditions. The researchers highlighted the molecular dynamics behind BMI1 upregulation and its crucial role in enhancing mitochondrial health. 

“Targeted brain delivery of nano-melatonin has shown remarkable results in both laboratory and animal models. Its potential to treat Parkinson’s and other related diseases makes it a promising candidate for clinical translation,” said Dr. Karmakar. 

Future studies will focus on large-scale clinical trials to evaluate the safety and efficacy of nano-melatonin in human subjects. The team is optimistic about its potential to establish nano-melatonin as a safer, more effective therapeutic option for millions affected by Parkinson’s and other disorders. 

Significance for Neurodegenerative Therapy 

This research underscores the critical role of Indian scientists in advancing the frontiers of neurotherapeutics. By addressing the challenges of drug delivery and bioavailability, the INST team has set a new benchmark in nanotechnology-driven medical innovation. 

Nano-melatonin’s success offers hope for improved treatment options, moving beyond symptomatic relief to address the underlying causes of Parkinson’s disease and related conditions. If proven effective in clinical trials, this breakthrough could transform the lives of millions worldwide, offering a new lease on life to patients struggling with debilitating neurological disorders.