BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: #Parkinson’s Disease

Promising Progress in Parkinson’s Treatment: The Role of Prasinezumab

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On April 17, 2024

In Student Post

Parkinson’s Disease, a neurodegenerative disorder affecting millions worldwide, has long remained a formidable challenge in the medical field. However, recent developments offer a glimmer of hope in the quest for effective treatment. A groundbreaking study led by Gennaro Pagano and his team at Roche Pharmaceuticals sheds light on a potential game-changer: prasinezumab, a drug designed to target the underlying culprit of Parkinson’s – the accumulation of misfolded alpha-synuclein proteins in the brain. Prasinezumab’s effectiveness in targeting misfolded alpha-synuclein proteins in Parkinson’s patients highlights the relevance of protein structure and function, a topic we have covered in class. Alterations in protein structure, such as misfolding, can disrupt normal cellular function and lead to the development of diseases like Parkinson’s.

Modeling the Molecular Basis of Parkinson's Disease

For years, researchers have recognized the pivotal role of alpha-synuclein in the progression of Parkinson’s disease. This misfolded protein wreaks havoc on dopamine-producing neurons, leading to the hallmark motor symptoms of the condition. While existing treatments aim to alleviate these symptoms by boosting dopamine levels, they fall short in addressing the root cause of the disease. Thus, the need for disease-modifying therapies that can slow or halt Parkinson’s progression remains urgent.

Enter prasinezumab, an innovative antibody engineered to bind to aggregated clumps of misfolded alpha-synuclein. Administered via intravenous infusion, this novel drug holds the potential to disrupt the neurotoxicity caused by alpha-synuclein, impede the spread of pathological aggregates between cells, and ultimately slow disease progression.

The pivotal clinical trial conducted by Pagano and his colleagues recruited 316 individuals with early-stage Parkinson’s disease. Participants received either a placebo or varying doses of prasinezumab over the course of one year. Initial results suggested minimal impact, but upon closer analysis, a ray of hope emerged.

Remarkably, prasinezumab demonstrated significant efficacy in individuals with more severe Parkinson’s symptoms. Those experiencing rapid eye movement sleep behavior disorder, taking MAO-B inhibitor, or rated at stage two on a symptom scale exhibited a notable reduction in the progression of motor symptoms compared to the placebo group.

This promising outcome suggests that prasinezumab may hold particular promise for individuals with rapidly progressing Parkinson’s, characterized by higher levels of misfolded alpha-synuclein in the brain. By potentially clearing these toxic protein aggregates, the drug could offer newfound hope for slowing disease advancement in this vulnerable population.

However, challenges remain on the path to conclusive validation. Critics point out the absence of biomarkers to monitor changes in alpha-synuclein levels within participants’ brains, raising questions about the drug’s disease-modifying effects. Vinata Vedam-Mai of the University of Florida Health highlights the need for longer-term data to assess both the safety and efficacy of prasinezumab comprehensively.

Looking ahead, further research is warranted to explore prasinezumab’s effectiveness in individuals with milder forms of Parkinson’s over extended periods. By exploring its potential across a broader spectrum of disease severity, researchers can unlock valuable insights into the drug’s therapeutic utility.

While the journey towards a definitive Parkinson’s treatment remains ongoing, the strides made with prasinezumab offer a beacon of hope for patients and researchers alike. With continued dedication and scientific inquiry, we inch closer to the elusive goal of transforming Parkinson’s disease from a life-altering diagnosis to a manageable condition. What do you think about the potential of prasinezumab? How do you think this can change the way we see a Parkinson’s diagnosis? 

 

The Blood Brain Barrier Can’t Block This!

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On April 23, 2023

In Student Post

University of Wisconsin-Madison Professor, Shaoqin “Sarah” Gong is ready to take on finding cures for brain disease such as Alzheimer’s and Parkinson’s disease. Gong and her colleagues strive to enable a “noninvasive, safe and efficient delivery of CRISPR genome editors” that can be used as forms of therapy for these diseases. According to MedlinePlus, there are many forms of brain disease, some caused by tumor, injury, genetics; however, Gong’s research focuses on degenerative nerve diseases. Degenerative nerve diseases can affect balance, movement, talking, breathing and heart function. The reason cures for degenerative nerve disease are difficult to create is because of the blood brain barrier. According to the American Society for MicroBiology, the blood brain barrier is a feature of the brain and central nervous system blocking the entrance of “microorganisms, such as bacteria, fungi, viruses or parasites, that may be circulating in the bloodstream”. Unfortunately, the barrier block is a very selective site that won’t let vaccines and therapies through. Fortunately, Gong’s nano-capsules with CRISPR’s genome editors point toward brain disease therapy and a cure.

 

Alzheimer's disease brain comparison

Gong’s study proposes dissolvable nano sized capsules that can carry CRISPR genome editing tools into organs. According to CRISPR Therapeutics, CRISPR technology meaning Clustered Regularly Interspaced Short Palindromic Repeats is an “efficient and versatile gene-editing technology we can harness to modify, delete or correct precise regions of our DNA”. CRISPR edits genes by “precisely cutting DNA and then letting natural DNA repair processes take over.” CRISPR targets mutated segments of DNA that can produce abnormal protein causing diseases such as degenerative nerve disease.  CRISPR works with the help of a guide RNA and Cas9. Together the complex can recognize and bind to a site next to a specific target sequence of DNA that would lead to the production of an abnormal protein. CAS9 can cut the DNA and remove a segment. As a result natural DNA pathways occur and RNA polymerase will return to rebuild and correct the mutated segment. 

via GIPHY

Consequently with the addition of glucose and amino acids the nano-capsules containing CRISPR Technology can pass through the blood brain barrier to conduct gene editing to target the gene for the amyloid precursor protein that is associated with Alzheimer’s. The topic of gene editing coincides with the Gene Expression portion of the AP Biology curriculum. In the topic of gene expressions 2 processes are emphasized: transcription (the process of making an RNA copy of DNA) and translation ( the process of making proteins using genetic information from RNA). In the CRISPR technology the editing of genes closely relates to the process of transcription. Transcription mistakes can be made which can lead to mutations, these mutations can potentially cause nonsense, missense or deletions of nucleotides ultimately producing wrong codons that would code for incorrect/abnormal proteins. However, the CRISPR technology would be able to correct these mutations in the DNA, replacing the incorrect nucleotides to correct ones and preventing the production of abnormal proteins. Fortunately, Gong’s unique nano-capsules have successfully been tested on mice, giving scientists hope that treatments and therapy for these brain diseases are coming soon and can help many.

Biological Warfare: Bacterial Edition

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On March 15, 2023

In Student Post

Ubiquitin cartoon-2-

In February 2023, a study was published announcing that bacteria possess something similar to humans that can activate and deactivate immune pathways, and therefore this “something” could be used to cure diseases; that “something” is called the ubiquitin transferase enzyme. 

Biological warfare, the use of infectious agents to kill diseases caused by other infectious agents, has been considered as a potential solution in the past. In fact, years prior, a family of DNA sequences now referred to as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) were discovered in bacteria, and it was determined that these sequences were capable of killing other phages and being used to cure infections. 

Our immune pathways, as we learned in our immunity unit in AP Biology, is crucial for our survival as a species. Our immune system consists of innate immunity, involving natural killer cells that serve as our first line of defense against pathogens, and adaptive immunity, involving B cells and T cells that need to be trained to fight these pathogens. Our immune pathways alone, however, cannot rid us of neurodegenerative diseases, and these diseases still unfortunately have no cure.. 

One may be wondering now, how can the ubiquitin transferase enzyme work to treat diseases like Parkinson’s? How does it help our immune pathways? Well, the answer to that is protein editing. The enzyme contains two proteins, CD-NTase-associated protein 2 and 3 (also known as Cap2 and Cap3); these proteins are what serve as the activation and deactivation for immune pathways: they can direct old, unnecessary, or damaged proteins to be broken down. 

When the potential of CRISPR was discovered, scientists used genome editing to direct the machine so it would kill its targeted diseases. A similar attempt could be made with the ubiquitin transferase enzyme. 

Finding the existence of this in bacteria especially is an amazing discovery, as not only does it propel us in the right direction in terms of potentially curing Parkinson’s or other neurodegenerative disorders, but it connects back to our other lesson in AP Biology that humans and bacteria are not so different after all. We share about a thousand genes!

It is particularly interesting knowing how biological warfare could be used to help us.

Environmental Cues Can Trigger Planned Movement and Advance Studies of Motor Disorders

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On March 22, 2022

In Student Post

A group of scientists from different universities, including Dr. Hidehiko Inagaki, Dr. Susu Chen, and Dr. Karel Svoboda, came together to understand how cues in our environment can trigger planned movement. Neurons in the human brain are active with diverse patterns and timing. The Motor cortex is responsible for the control of movement. The patterns of the motor cortex differ in the phases of movement. The transitions between these phases is a critical part of movement. The brain areas controlling these transitions were a mystery.

To identify the parts of the brain controlling these transitions the group of scientists performed their research on mice.They recorded the activity of neurons in a mouse’s brain when doing a triggered movement task. Researchers found brain activity taking place directly after the go cue and between the stages of movement. This brain activity came from a circuit of neurons in the midbrain, thalamus, and cortex. To determine whether this circuit was a conductor or not the scientists used optogenetics. Through the use of optogenetics Dr. Inagaki and his colleagues were able to identify a neural circuit critical for triggering movement in response to environmental cues. Dr Inagaki says that “We have found a circuit that can change the activity of the motor cortex from motor planning to execution at the appropriate time. This gives us insight into how the brain orchestrates neuronal activity to produce complex behavior.

Figure-1

Not only is this important for the use of knowing more about the brain but it also helps to advance studies of motor disorders, such as Parkinson’s disease. By adding environmental cues to trigger movements it could drastically change the mobility of patients.

In Ap Biology class we learned about cell communication. Neurons communicate with each other by releasing specific molecules in the gap between them, called the synapses. The sending neuron passes on messages through neurotransmitters that are picked up by the receptors of the receiving neuron.

Could Overproducing A Gene Prevent Parkinson’s Disease?

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On March 20, 2022

In Student Post

A team from the University of Geneva (UNIGE) discovered a gene that, when overexpressed, prevents the development of Parkinson’s disease in fruit flies and mice. Parkinson’s disease is a movement disorder caused by a brain disorder. Parkinson’s disease symptoms typically appear gradually and worsen over time. Men are affected by the disease at a rate that is roughly half that of women. A combination of genetic and environmental factors contributes to the disease’s underlying cause.

Emi Nagoshi, Professor in the Department of Genetics and Evolution at the UNIGE Faculty of Science, studies the mechanisms of dopaminergic neuron degeneration using the fruit fly. The midbrain dopaminergic neurons are the primary source of dopamine in the central nervous system. Their absence is linked to Parkinson’s disease. Emi’s test connects to the Fer2 gene, whose human homolog encodes a protein that regulates the expression of many other genes and whose mutation may lead to Parkinson’s disease through unknown mechanisms. 

The absence of Fer2 causes Parkinson’s disease-like symptoms, the researchers investigated whether increasing the amount of Fer2 in the cells could provide protection. When flies are exposed to free radicals in their environment, such as toxins, their cells undergo oxidative stress, which leads to the degradation of dopaminergic neurons. By creating mutants of the Fer2 Homolog in mouse dopaminergic neurons, the scientists were able to show that oxidative stress has no negative effect on the flies if they overproduce Fer2, confirming the hypothesis of its protective role. They discovered abnormalities of these neurons, as well as defects in movement patterns in aged mice, just as they did in the flies.

Alleles on gene

Genes can have alleles, which give different traits to different people.

In comparison with our unit, the Fer2 provides the understanding of how the molecules that make up cells determine the behavior of in this case mice and fruit flies. Each is made up of nucleotides that are arranged in a linear fashion that resides in a specific location on a chromosome. Most genes encode for a specific protein or protein segment that results in a specific characteristic or function, such as providing a protective barrier towards Parkinson’s disease.

 

 

 

Eating Shark Meat Increases Your Chance At Developing Alzheimer’s Disease

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On October 24, 2020

In Student Post

What toxins lie beneath the grey leathery skin of a shark? 

According to the article written at the University of Miami Rosenstiel School of Marine & Atmospheric Science,  scientists found toxins that are commonly linked to neurodegenerative diseases in the fins and muscles of many different types of sharks. Scientists collected samples of ten different sharks that are commonly found in the Atlantic and Pacific Ocean. The samples came back and tested positive for two toxins: mercury and beta-N-methylamino-L-alanine(BMAA). Many studies have linked mercury and BMAA to diseases like Alzheimer’s and amyotrophic lateral sclerosis(ALS). Shark meat delicacies are common in many Asian countries with dishes including shark fin soup.

Effects of Mercury on humans

Mercury has numerous health effects on humans and can be detrimental to one’s neurological system. Not only that, mercury also affects digestive and immune systems and can damage lungs, kidneys, skin and eyes. Mercury poisoning can also cause slow reflexes, damaged motor skills and intelligence disorders. In many instances, mercury poisoning can increase your chance at developing Alzheimer’s disease. Researchers found that the toxin mercury tends to accumulate in the shark’s tissue throughout their lives.

Effects of beta-N-Methylamino-L-alanine (BMAA) on humans 

The neurotoxin beta-N-Methylamino-L-alanine is an amino acid produced by certain organisms that have been linked to ALS, amyotrophic lateral sclerosis. BMAA was also linked to being a cause of Parkinson’s disease. Researchers found BMAA in shark fins and cartilage both of which are used in food and medicine, respectively. The image shown below is of alanine, one of the amino acids. There is an NCC structure shown in the middle, a carboxyl group on the left hand side, an amine group on the right hand side and the CH3 represents the R group. Since BMAA is a non-protein amino acid, when inserted with other amino acids it releases toxic chemicals. The picture below represents an alanine amino acid, however, BMAA has a slightly different structure. The R group of BMAA is NH along with H3C and the amine group is NH2 which contributes to its toxicity.

Why you shouldn’t eat shark meat? 

If the reasons above have not convinced you not to eat shark meat, many species of sharks are facing extinction due to the high demand for shark parts. Though each of these toxins have their own set of dangers, mercury and BMAA together can have an entirely different and more dangerous effect on humans that researchers have not yet explored. To be safe one should refrain from consuming shark products if not for your own health but to save the sharks.

Don’t be afraid of sharks we need them! 

Sharks play a very important role in the ecosystem. Sharks are the apex predators in marine life are most likely at the top of the food chain. Ultimately, they keep the rest of the ocean healthy and in order. Without them many dangerous organisms would be present and could harm marine life. Sharks keep balance within the ecosystem and ensures diversity among ocean species. If you suffer from viruses like cystic fibrosis, researchers are close to finding anticoagulants within shark tissue that could possibly cure certain diseases. Sharks are also very important in the carbon cycle. When they die naturally, their bodies are full of carbon which is then consumed by scavengers and carbon is recycled into the ecosystem. Sharks do way more for us than we think!

CRISPR Cas-9 is the New Key to Curing Parkinson’s Disease

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On March 10, 2018

In Student Post

A new screening tool for Parkinson’s Disease was just discovered by a team of researchers at the University of Central Florida. They did this by using cutting edge gene-editing technology, CRISPR Cas-9, which allows scientists to detect levels of alpha-synuclein, a brain protein associated with Parkinson’s.

What is alpha-synuclein?

This protein can be found in our brain, it is something all humans have. When someone develops Parkinson’s, the levels of this protein become abnormal. This protein can become dangerous to neurons and kill them. This person would gradually loose brain cells, affecting their motor functions.

What is CRISPR Cas-9?

CRISPR Cas-9, Clustered Regularly Interspaced Short Palindromic Repeats, is a gene-editing system that enables scientists to edit DNA while preserving the cell. Instead of extracting all of the proteins from a cell and measuring them, CRISPR Cas-9 allows us to edit one gene.

How is used?

The specific gene the team wanted to edit was the alpha-synuclein. The CRISPR Cas-9 helped them edit the gene and add a luminescent tag, made up of similar proteins that make fireflies glow, in order to track how much of this protein is produced in a brain cell. When the brain cell produces alpha-synuclein, it glows, making it easier to visualize once the cell is in a diseased state. Furthermore, scientists can treat these cells with different medications, whether or not they glow will tell if the medications tested are successful.

The Future:

Engineered cells and light detection are a great duo for the future of researchers. Light detection on these engineered cells is helpful for high throughput screening where multiple drugs can be tested at the same time. This research can potentially lower the number of Parkinson’s cases per year. Currently, 60,000 new cases are reported per year in just the United States! Could these numbers drop in the future? Can CRISPR help find a cure to other diseases as well? Reading this article opened my mind to the endless possibilities CRISPR unlocked, I am excited to see where else it could take science.

 

 

 

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