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New Approaches in Parkinson’s Disease Treatment

Researchers explore new delivery systems for neurotransmitters in treating Parkinson's disease.

Payal Vaswani, Krupa Kansara, Ashutosh Kumar, Dhiraj Bhatia

― 6 min read


Innovative Strategies for Innovative Strategies for Parkinson's Care challenges effectively. New methods aim to tackle Parkinson’s
Table of Contents

Parkinson’s disease (PD) is a condition that mainly affects the brain and is quite common, being the second most frequent neurodegenerative disorder. Around 6 million people worldwide are living with this disease. The main issue in PD is that a certain protein called Alpha-synuclein builds up in the brain, forming clumps known as Lewy bodies. These clumps mess with how brain cells work, leading to various symptoms.

Symptoms of Parkinson’s Disease

The symptoms of PD are typically split into two groups: motor symptoms and non-motor symptoms.

Motor Symptoms

The motor symptoms include:

  • Tremors: Shaking that can involve hands or other parts of the body.
  • Bradykinesia: Slowness of movement that makes everyday tasks take longer.
  • Rigidity: Stiffness in the muscles.

These symptoms can make moving around and doing everyday things much harder.

Non-Motor Symptoms

Non-motor symptoms can also appear, sometimes even before the motor issues start. These can include:

  • Anxiety
  • Depression
  • Sleep problems

These symptoms can be quite distressing too, making PD more than just a movement disorder.

Current Treatment Options

The usual treatment for PD involves a medication called levodopa (L-DOPA). This is a substance that the body turns into dopamine, a chemical that helps with movement. While L-DOPA can help improve motor symptoms, it has some downsides. Over time, long-term use can lead to a condition called levodopa-induced dyskinesia (LID), where patients experience uncontrolled movements. This can make life quite challenging.

The Need for New Treatments

Because of the limitations and side effects associated with current treatments, scientists are on the lookout for new ways to help those with PD. It’s kind of like searching for the Holy Grail but with more lab coats and fewer knights.

The Role of Neurotransmitters

Neurotransmitters are messengers in the brain that help with communication between cells. Some key neurotransmitters involved in PD include dopamine, serotonin, epinephrine, and norepinephrine. While L-DOPA focuses on balancing dopamine levels, the other neurotransmitters might also have roles that haven’t been thoroughly investigated yet. For example, norepinephrine has shown that it can protect neurons in certain situations.

As researchers dig deeper, they’ve found that serotonergic neurons might also play a part in PD. This has led to more studies focusing on the roles of serotonin, epinephrine, and norepinephrine in PD treatment.

The Rise of DNA Nanotechnology

In the quest for new therapies, DNA nanotechnology is emerging as a promising option. One interesting tool in this field is a structure called DNA tetrahedron (TD). Think of it as a tiny delivery truck built from DNA that can transport helpful substances into cells.

One of the benefits of using TD is that it is small, biocompatible (meaning it plays nice with the body), and easy to make. There’s even evidence that it can cross the blood-brain barrier, a protective shield that keeps certain substances from entering the brain. This characteristic could be crucial for delivering treatments for PD, especially if serotonin itself can’t cross this barrier.

The Research Study

In a recent study, researchers aimed to look at how serotonin, epinephrine, and norepinephrine might help with PD. The plan was to use TD as a delivery system for these neurotransmitters and see if they could help reduce the accumulation of alpha-synuclein in cells.

Step 1: Making the Delivery System

First, the researchers created the DNA tetrahedron (TD) using a simple process. They mixed four strands of DNA and let them form the desired shape. Then, they checked to make sure it looked right using various techniques. They found that TD had a small size of about 13.3 nanometers (just a tiny speck!) and was shaped like a triangle.

Next, they loaded the TD with the neurotransmitters they picked: serotonin, epinephrine, and norepinephrine. They found that TD could hold these neurotransmitters without any problems, suggesting that it was ready for the next step.

Step 2: Testing the System

To see if their system worked, the researchers used a model involving PC12 cells, a type of cell often used in PD research. They treated these cells with a substance called MPTP, which is known to cause problems that mimic PD.

They found that the TD loaded with neurotransmitters could enter the cells without much trouble. It seemed that the neurotransmitters leaped onboard for the ride into the cells. To check if they were actually working, the researchers looked for signs of alpha-synuclein clearance.

In their tests, they discovered that TD loaded with serotonin effectively reduced the problematic accumulation of alpha-synuclein. TD loaded with norepinephrine also showed some promise in fighting this buildup. Meanwhile, the TD loaded with epinephrine didn’t perform quite as well.

Step 3: Tackling Reactive Oxygen Species

When cells are under stress, they can produce a lot of reactive oxygen species (ROS), which are harmful and can lead to cell damage. In their studies, the researchers found that MPTP treatment led to an increase in ROS levels. However, treatment with TD and TD loaded with serotonin significantly reduced these levels of ROS.

Mitochondria, the powerhouses of cells, are vital for energy and can also produce ROS. The team investigated the effects on mitochondrial health and found that their treatment helped boost mitochondrial mass and reduce the harmful ROS in these tiny power plants.

Step 4: Addressing Ferroptosis

Ferroptosis is a type of cell death that can happen when there’s too much iron and lipid peroxidation in cells. In their tests, the researchers discovered that MPTP treated cells had increased iron levels, but treatment with TD systems effectively reduced this toxic iron accumulation.

Lipid peroxidation, which can also be damaging, was tested using a special sensor. Again, the treatment with TD:Ser helped lower the levels of lipid peroxidation, a positive outcome for cell health.

Moving to In Vivo Studies

Lastly, researchers wanted to see if their successful in vitro findings would hold true in living organisms. They turned to zebrafish, which are often used in research because they have similar biological processes to humans. They treated the zebrafish with MPTP and then gave them TD loaded with the neurotransmitters.

The results continued to look promising as TD:Ser effectively reduced ROS levels in the zebrafish model, confirming that their delivery system could potentially work in living beings.

Conclusion: A New Hope for Parkinson’s Disease Treatment

In summary, the study dives into the exciting possibility of using a new delivery system with neurotransmitters to tackle Parkinson’s disease. By focusing on clearing alpha-synuclein, reducing ROS, and easing iron and lipid issues, researchers are opening doors to new therapeutic options. Although there is much work ahead, the potential of combining DNA nanotechnology with neurotransmitter strategies offers a bright glimmer of hope for better treatments for those affected by this challenging condition.

So, next time you hear about Parkinson’s disease, remember that researchers are working hard to find solutions, and who knows? One day, we might have much better treatments that could turn the tide in this ongoing battle. After all, even the toughest problems can sometimes find a little humor in the science of solutions.

Original Source

Title: Neurotransmitter loaded DNA nanocages as potential therapeutics for α-synuclein based neuropathies in cells and in vivo

Abstract: Parkinsons disease is one of the neuropathies characterized by accumulation of -synuclein protein, leading to motor dysfunction. Levodopa is the gold standard treatment, however, in long term usage, it leads to levodopa induced dyskinesia (LID). New therapeutic options are need of the hour to treat the -synuclein based neuropathies. The role of imbalance of neurotransmitters other than dopamine has been underestimated in -synuclein based neuropathies. Here, we explore the role of serotonin, epinephrine and norepinephrine as a therapeutic moiety. For the efficient in vivo delivery, we use DNA nanotechnology-based DNA tetrahedra that has shown the potential to cross the biological barriers. In this study, we explore the use of DNA nanodevices, particularly DNA tetrahedron functionalized with neurotransmitters, as a novel therapeutic approach for MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced Parkinsons disease in PC12 cellular system. We first establish the effect of these nanodevices on clearance of -synuclein protein in cells. We follow the study by understanding the various cellular processes like ROS, iron accumulation and lipid peroxidation. We also explore the effect of the neurotransmitter loaded nanodevices in in vivo zebrafish model. We show that neurotransmitter loaded DNA nanocages can potentially clear the MPTP induced -synuclein aggregates in cells and in vivo. The findings of these work open up new avenues for use of DNA nanotechnology by functionalizing it with neurotransmitters for future therapeutics in treatment of neurodegenerative diseases such as Parkinsons disease. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/626934v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): [email protected]@a08756org.highwire.dtl.DTLVardef@1153704org.highwire.dtl.DTLVardef@1cefebb_HPS_FORMAT_FIGEXP M_FIG C_FIG TD:NT can clear -synuclein by targeting the ferroptosis pathway.

Authors: Payal Vaswani, Krupa Kansara, Ashutosh Kumar, Dhiraj Bhatia

Last Update: 2024-12-09 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.12.04.626934

Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.04.626934.full.pdf

Licence: https://creativecommons.org/licenses/by-nc/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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