New method found to inhibit Parkinson’s disease

Contrary to earlier discovery that a chemical found in a synthetic opioid, MPTP, induced a form of Parkinson's disease, a new study has found that it is an enzyme in the body that can metabolise compounds formed in the brain from alkaloids causing a neurodegenerative condition in mice.

The study  suggested that the enzyme, mitochondrial CYP2D6, presents a potentially powerful new target for Parkinson's treatment. "Over the past two or three decades, researchers have tried inhibiting the process by they believed MPTP was metabolised, with mixed success," he said.

"We believe that mitochondrial CYP2D6 is the more direct drug target, which might prove better in treating idiopathic Parkinson's disease," added one of the researchers. The study investigated the mechanism of Parkinson's disease when a specific cause cannot be pinpointed.

Previous studies have shown that MPTP and similar toxic compounds induce Parkinson's disease in rodents and primates. The mechanism of action, as scientists understood it, involved the compounds being oxidised to form MPP+, a toxic metabolite.

The enzyme that was believed to be responsible is called monoamine oxidase B (MAO-B), present in the nervous system's glial cells. In that conception of the mechanism, MPP+ was thought to then be transferred to dopamine neurons by dopamine transporter proteins, and, indeed, Parkinson's is characterised by unusually low dopamine levels in the brain.

Researchers have tried to stem the effects of Parkinson's by targeting two players in this presumed pathway, both MAO-B and the dopamine transporter protein, with only mixed success. In earlier work, Avadhani and colleagues had shown that the enzyme CYP2D6, localised to the body's energy factories, the mitochondria, could play a role in metabolising MPTP to MPP+.

In the new investigation, they took a closer look at beta-carbolines and isoquinolines, toxins that resemble MPTP which the body produces from substances found in tobacco smoke, alcohol, and some foods.

They found that, instead of MAO-B, it was mitochondrial CYP2D6 that activate the beta-carbolines and isoquinolines inside the dopamine-producing neurons, rather than the glial cells. This route of activation, in a mouse model, results in neuronal damage and oxidative stress, symptoms akin to Parkinson's. "CYP2D6 is known to play a role in influencing the activity of a number of drugs," said a researcher.

In an attempt to target this pathway, the researchers showed that mice lacking CYP2D6 did not exhibit severe symptoms than mice with the protein did. In addition, an inhibitor of CYP2D6 prevented neuronal damage in the mice.

"The CYP2D6 inhibitor ajmalicine is a member of the reserpine family of alkaloids, found in the plant Rauwolfia serpentine and was long used in India for treating mental illness, such as paranoia and schizophrenia," he said. "Mitochondrial targeting of such compounds is likely to be effective in treating Parkinson's patients, and pursuing that is our future strategy," said the researcher.

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Cancer growth in the body could originate from a single cell – target it to revolutionise treatment

Cancer remains a frightening and largely incurable disease. The toxic side effects of chemotherapy and radiation make the cure often seem as bad as the ailment, and there is also the threat of recurrence and tumour spread.

Cancer treatment still follows a practically medieval method of cut, burn or poison. If the growth can’t be cut out through surgery, it may be burnt away with radiation or poisoned by chemotherapy. As a result, cancer therapy remains a daunting diagnosis for patients and treatment options seem limited for a disease which causes one in 6 deaths globally.

The failure to innovate in cancer treatment may lie in the very poor success rate of clinical trials. Approximately 95%-98% of new anti-cancer drugs actually fail phase III clinical trials, the phase in which new treatments are compared with existing therapy options. This is a staggering statistic. No other business could possibly survive with such an abysmal success rate.

Most drugs are made to target “bulk” cancer cells, but not the root cause: the cancer stem cell. Cancer stem cells, also known as “tumour-initiating cells”, are the only cells in the tumour that can make a new tumour. New therapies that specifically target and eradicate these cancer stem cells are needed to prevent tumours growing and spreading, but for that there needs to be more clarity around the target.

Our new research may have discovered such a target. We have identified and isolated cells within different cancerous growths which we call the “cell of origin”. Our experiments on cancer cells derived from a human breast tumour found that stem cells – representing 0.2% of the cancer cell population – have special characteristics.

They generate vast amounts of energy and proliferate rapidly. We believe that they resemble the cancer cell of origin that has escaped senescence – the natural process of cell ageing and “death” which concludes a healthy cell life cycle. These are thought to be the first cancer cells which start the process of uncontrolled cell multiplication and cause tumours to form.

These cancer stem cells undergo anchorage-independent growth, also known as growth in suspension, without any tissue attachment. This is how metastasis occurs – spreading via the blood vessels and lymphatic vessels. These features put them front and centre as a new target for anti-cancer therapy.

With astonishing luck, these energetic cancer stem cells are colour-coded which means they have a natural phosphorescent glow, making them easy to identify and target.

Now that we have found them and we know how they behave, it should be relatively simple to find drugs to target cancer stem cells. In our new paper we have already shown that they are easily targeted with a mitochondrial inhibitor or a cell cycle inhibitor such as Ribociclib, an FDA-approved drug in the US which would prevent their proliferation. 

Ultimately, this means that if we focus on energetic cancer stem cells, we may be able to directly hit the target. We might be able to turn cancer into a manageable chronic disease, like diabetes. We believe that we have arrived at the start of a new, more fruitful, road in cancer therapy. As a consequence, “big pharma” drug screening should actually focus on cancer stem cells and their relevant targets.

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Health Benefits of Cayenne Pepper and Capsaicin

Much has been written about the healing power of Cayenne pepper, and its reputation continues to grow among researchers and practitioners of alternative medicine, but surprisingly many people are still unaware of the health benefits of its consumption and the wonders of its powerful active ingredient, capsaicin.
The cayenne pepper itself is a spicy red pepper named after the capital of French Guiana and is considered to have a medium-high intensity with a slightly stronger intensity than that of jalapeño and tabasco peppers. The reason for this is its relatively high capsaicin content, which gives it its sharp flavor and also a plethora of health benefits that are well worth knowing.

1. Fights cancer

Over the years, a large number of articles and studies have been published that have proven the strength of cayenne pepper and similar hot peppers against cancerous tumors. In 2004, a team of researchers successfully treated pancreatic cancer cells with capsaicin. The researchers found that the compound interferes with the mitochondrial activity of the cancer cells (an organelle in the cell responsible for producing energy and storing and preserving hereditary material) and leads to the cellular death of damaged parts of the body without damaging the normal pancreatic cells.
In a 2006 article it was found that the strong capsaicin compound was able to destroy about 80 percent of prostate cancer cells in laboratory mice. There is no shortage of other examples of experiments and tests among people and animals alike, which have shown similar results when it comes to other cancers such as leukemia and lung cancer.

2. Treats bleeding hemorrhoids

Cayenne pepper and similar spicy foods are a magic cure when it comes to bleeding hemorrhoids. People who have suffered hemorrhoids for years and are at risk of death as a result of the problem report that the bleeding stopped after consuming cayenne tea made from a teaspoon of cayenne powder and a quarter cup of hot water. I, for example, suffered from bleeding hemorrhoids for 11 years. I underwent three surgical interventions that didn’t really work and I seriously considered undergoing thorough surgery to completely remove my hemorrhoids because my condition became critical due to blood loss on a daily basis. Cayenne tea stopped the bleeding immediately. The hemorrhoids themselves contracted to a minimum after about two weeks, says the author of this article.
Because cayenne is rich in anti-inflammatories and other essential ingredients, it helps the body overcome the itching, swelling, and pain caused by hemorrhoids, and it also helps restore the elasticity of veins and arteries. Some people recommend applying cayenne pepper creams to the affected area to treat hemorrhoids, but this method is very uncomfortable and consuming it as a drink or seasoning your food with it is a much better alternative.

3. Improves the functioning of the circulatory system and the heart

Cayenne peppers contribute greatly to heart health on two main levels: the first is related to their direct positive effect on various factors that affect the health and normality of this important muscle, such as blood pressure and cholesterol levels in the body.
Second, because of their effect on the veins and arteries mentioned in the previous section, cayenne peppers and other foods containing capsaicin help prevent atherosclerosis and reduce the risk of developing dangerous blood clots. Given these significant benefits, it is not surprising that many large and respected bodies are studying the possibility of using capsaicin-based products to treat heart disease and arrhythmia. 

4. Treats headaches and migraines

Cayenne peppers and other spicy foods provide a natural and simple way to overcome headaches. There is even a wealth of evidence from people who have suffered from constant migraines and have found that eating hot peppers helped them regain control of their lives and soothe the most severe headaches.
The reason for this is the ability of the active ingredient in these peppers, capsaicin, to reduce the levels of the chemical that allows the transmission of pain sensation in the brain, Substance P. When the levels of this chemical are reduced, we feel much less pain. This effect can be achieved by eating foods with cayenne pepper, drinking a teaspoon of ground cayenne pepper mixed in a glass of water, and also by using external creams with a high concentration of capsaicin.

5. Helps the digestive system

Although caffeine and similar spicy foods often have an appetite suppressing effect on people who consume them, their consumption generally helps the digestive process and encourages the secretion of gastric acids that allow us to effectively break down the food we eat. Consuming cayenne peppers encourages faster metabolism and helps the liver and gallbladder rid the body of toxins and harmful substances quickly and easily. In addition, the findings of a 2011 study proved that the consumption of hot peppers raises body temperature and helps burn calories, information that anyone who wants to lose a few pounds and enjoys spicy food, would certainly be happy to discover.

6. Helps in recovery from various winter diseases

And finally, an important health benefit of cayenne peppers, which we recommend taking advantage of in the current winter. This powerful dish provides us with a wealth of powerful components that help our bodies fight various winter diseases, especially colds and throat infections. Drinking hot water with cayenne pepper powder is an excellent way to quickly calm a sore throat while eating it provides quick relief of a stuffy nose.

How much cayenne pepper should you consume?

First, it is important to mention that many of the health benefits mentioned are the product of consuming foods that contain capsaicin, such as cayenne pepper. You can enrich your menu with this healthy organic compound using a wide variety of other spicy foods and also foods like mustard, garlic, and ginger. If you are not used to spicy foods, it is recommended to start by eating peppers that have 30,000 units of heat on the Scoville scale (a scale measuring the sharpness of peppers based on the capsaicin content ranging from 0 to 16 million).
If you are dealing with ground peppers, you can add about a quarter of a teaspoon to a quarter cup of hot water, mix and drink quickly. The process of getting used to the spiciness is very fast, and within a month you’ll easily be able to drink a full teaspoon of cayenne powder with the same amount of water and even gradually switch to peppers with 90,000 Scoville units. For those who are scared of a little spice, you can also swallow cayenne capsules; the positive effect on your health will be weaker but still significant. In any case, you should always consume cayenne with food and if you choose to simply eat hot peppers in their natural form, you can add them to a plethora of dishes such as fish and rice.

THIS IS ONLY FOR INFORMATION, ALWAYS CONSULT YOU PHYSICIAN BEFORE HAVING ANY PARTICULAR FOOD/ MEDICATION/EXERCISE/OTHER REMEDIES.                                                                                
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Dark chocolate may protect your brain from ageing

Chocoholics, take note! Eating dark chocolate may protect your brain from age-related stress and inflammation that are thought to play an important role in the neurodegenerative disorders such as Alzheimer’s disease. 

The findings may help explain the beneficial effects on memory seen in people who consume dark chocolate, researchers said. 

Oxidative stress and inflammation increase with ageing and are thought to play an important role in the development of neurodegenerative diseases such as Alzheimer’s disease. 

In a new study, researchers from the University of California San Diego in the US showed that the epicatechin (Epi), a flavanol found in foods such as dark chocolate, reduced damaging oxidative stress and neuro-inflammation in a mouse model of ageing. 

Just two weeks of treatment with epicatechin not only suppressed levels of oxidative stress and neuro-inflammation that would normally be increased in this mouse model, but also improved memory and anxiety levels in the mice. 

“We previously reported on the beneficial effects of treatment with the cacao flavanol on ageing-induced oxidative stress and capacity to restore modulators of mitochondrial biogenesis in the prefrontal cortex of 26-month-old mice,” researchers said. 

“In the current study, using a similar mouse model of ageing, we examined the capacity of Epi to mitigate hippocampus oxidative stress and inflammation leading to improved memory and anxiety levels,” they said. 

Male mice underwent two weeks of treatment and samples of their brains were collected for the assessment of relevant endpoints. The assessment of the OS markers protein carbonyls and malondialdehyde levels show significant increases with ageing that are suppressed by Epi. 

Altogether, results evidence a unique capacity of Epi to significantly mitigate neuro-inflammation leading to improved brain function. The research was published in the journal Experimental Biology. 

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Altered mitochondrial DNA linked to autism

Children diagnosed with autism spectrum disorder (ASD) have greater numbers of harmful mutations in their mitochondrial DAN  (mDNA) than family members, US researchers have found.

Autism is a serious developmental disorder that impairs the ability to communicate and interact. 

Previous studies pointed out to the malfunctions in mitochondria -- the powerhouse of the cell -- as a major cause of ASD, however, the biological link was not established.

In the new study, the researchers discovered a unique pattern of heteroplasmic mutations, where both mutant and normal mDNA sequences exist in a single cell.

Children with ASD have more than twice as many potentially harmful mutations compared to unaffected siblings, and 1.5 times as many mutations that would alter the resulting protein.

"The result of our study synergises with recent work on ASD, calling attention to children diagnosed with ASD, who have one or more developmental abnormalities or related co-morbid clinical conditions for further testing on mDNA and mitochondrial function," said Zhenglong Gu of Cornell University in Ithaca, New York.

Further, the study showed that these mutations can be inherited from the mother, or could be a result of spontaneous mutation during development.

Carrying harmful mutations in mDNA is also associated with increased risk of neurological and developmental problems among children with ASD, because mitochondria plays a central role in metabolism.

The risks are most pronounced in children with lower IQ and poor social behaviour compared to their unaffected siblings, the researchers said.

"Since many neurodevelopmental disorders and related childhood disorders show abnormalities that converge upon mitochondrial dysfunction, and may have mDNA defects as a common harbinger, future research is needed...," Gu noted.

For the study, published in the journal PLOS Genetics, the scientists analysed mDNA sequences from 903 children with ASD, along with their unaffected siblings and mothers.

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