People have been consuming tobacco for millennia, though it wasn't until the late 1820s that nicotine was first extracted from tobacco plants.

Now, 200 years later, scientists have finally discovered how the tobacco plant makes those nicotine molecules.

The discovery could potentially transform products made from or using tobacco species, a practice known as 'plant molecular farming'.

Scientists have been engineering tobacco plants to produce therapeutic compounds and even vaccines, but the nicotine is problematic: it's highly addictive.

Understanding how nicotine is made could mean researchers could devise ways to prevent its production in plants.

"It is a big moment in plant science and biochemistry that we now have the answer we have been chasing for more than 200 years," says biologist Benjamin Lichman, from the University of York.

Lichman and colleagues at the University of Copenhagen in Denmark identified in their new study the genes and enzymes that help produce nicotine.

"With this new knowledge we can remove or repurpose the nicotine that is produced naturally by the plant and create better biotechnology tools," says Lichman.

"There is also exciting potential for the future to adapt tobacco's nicotine forming system to make useful pharmaceutical compounds."

Through a genetic analysis of tobacco (Nicotiana tabacum), the researchers flagged genes that sit close together in tobacco DNA, and activate at the same time as genes already known to be involved in nicotine production.

They then isolated the enzymes produced by these genes.

In both test tubes and living plants, the researchers demonstrated that these enzymes combined to form nicotine.

It turns out the enzymes work through a clever process that goes some way to explaining why they've remained hidden for so long.

Initially, a glucose molecule is attached to the building blocks of nicotine, putting them in the reactive state that's needed for nicotine assembly. That same molecule then snaps off after the process has finished – so the sugar does its essential job, then disappears.

The researchers also identified the two enzymes, NaGR and NicGS, that help assemble the nicotine molecule from its raw materials. Those materials are an amino acid linked to protein building and a vitamin-like compound.

"It is exciting because it has real-world applications," says Lichman.

"A close relative of tobacco, Nicotiana benthamiana, is already used in 'molecular farming' to produce life-saving drugs and vaccines."

"It opens up new ways to use tobacco plants for good: not in cigarettes, but for medicines and other valuable products."

Another recently published study backs up the findings: nicotine is created by glucose, helped by a chain of enzymes, before the glucose disappears.

That complete vanishing act, together with the unusual way glucose is used here compared to other plant processes, is what made the nicotine production process so elusive for so long, the researchers say.

There are still some questions about nicotine production in tobacco, but we now have the main steps and key ingredients sorted.

The researchers suggest the process could be tweaked to produce different chemical substances and tobacco with low levels of nicotine; however, previous attempts have stunted plant growth.

Related: Plants Stopped Thriving When Earth Warmed 56 Million Years Ago

Ultimately, these researchers have not only solved a 200-year-old mystery but also laid the groundwork for more advanced and precise bioengineering.

"Tobacco plants can be used in biotechnology as platforms for producing vaccines or other pharmaceutical products, but it is plagued by the presence of nicotine, which contaminates the products and requires processing to remove it," says Lichman.

The research has been published in Nature Communications.

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A diet designed for weight loss could offer a different bonus benefit, according to a new review.

Researchers from the University of Coimbra in Portugal looked at dozens of previous studies analyzing this diet and its relationship to neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's disease.

If you're on the ketogenic (or keto) diet, you'll be prioritizing fats and proteins, while cutting down on carbohydrates – and it turns out, at the same time you could be protecting your brain from disease.

The team also looked at research relating to the keto diet more generally, trying to pin down the effects of the high-fat, dairy-rich diet on the body's metabolism – how it stores and uses energy in the form of glucose (sugar).

Problems with processing glucose underpin several brain diseases, and the team concluded that the keto diet has real potential as a way of targeting these conditions.

They also acknowledge there are several challenges with using the diet as a treatment method.

"The ketogenic diet has emerged as a metabolically oriented strategy with potential preventive and therapeutic relevance in neurodegenerative diseases," write the researchers in their published paper.

"While preclinical studies have demonstrated encouraging results, significant gaps remain in understanding long-term effects, safety, and practicality of [the ketogenic diet] in clinical settings."

The keto diet works by getting the body to burn fat for energy rather than glucose (which we get mainly from carbohydrates). Biologically, this is known as a metabolic state called ketosis, where fat molecules called ketones are used instead of glucose.

It means weight can rapidly be lost, and the keto diet is actually prescribed for treating epilepsy in some cases.

As the researchers here summarize, there are multiple mechanisms through which it might protect against neurodegenerative conditions too.

Brains running on empty could use ketones as an alternative, emergency energy source, for example, as has been demonstrated in studies of Alzheimer's – thus going some way to restoring neuron stability and functionality.

Ketones have also been shown to reduce inflammation in mice models of Parkinson's and multiple sclerosis, boost an important cellular clean-up process called autophagy, and promote gut bacteria associated with better brain function.

Add all of that up, and there's plenty of evidence that the keto diet – and the metabolic changes that it brings about – can target some of the processes thought to contribute to several devastating brain diseases.

"The ketogenic diet may serve as a complementary metabolic intervention that supports disease-specific treatments by enhancing metabolic resilience and contributing to symptom management," write the researchers.

It's not quite as simple as using the keto diet with people at high risk of neurodegenerative problems, however. Most of the reviewed studies involved animals rather than people, so further investigation is required in terms of clinical trials.

The keto diet is also one of the most difficult to stick to, so getting patients to follow it might be a problem. It also tends to come with a variety of unpleasant side effects: it's been linked to constipation, insomnia, and high cholesterol in some people, for instance.

Past studies have found that the keto diet might cause harm in the longer term, and increase the risk of type 2 diabetes and heart disease. These downsides need to be weighed against any benefits that come along with the keto diet.

What this new review does is give us a 'state of play' in terms of scientific understanding right now. The multiple studies that were looked at offer solid evidence that following a keto diet and having better brain health are connected – though their results shouldn't be considered in isolation.

Related: Keto Diet May Have a Surprising Bonus Benefit, Mouse Study Suggests

"This review underscores the potential of [the ketogenic diet] for treating neurodegeneration on the basis of current scientific evidence while highlighting the need for further research to optimize its application and address existing gaps," write the researchers.

The research has been published in Translational Neurodegeneration.

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A diagnosis of multiple sclerosis (MS) comes with a wave of uncertainty about how the condition will progress.

Now, new research points to a potential mechanism and treatment target for those who are most severely affected.

MS damages nerve cells, stripping away their protective covering that keeps nerve signals firing.

The new study, from researchers in the Netherlands, suggests that in the most severe cases of MS, an immune cell usually in charge of repairing damaged tissue and clearing away waste becomes overloaded with fat droplets.

Known as "foamy microglia", these cells have been spotted in MS patients before, but it wasn't clear exactly what they were doing.

According to the findings from this latest study, they could be key drivers of MS at its worst.

MS is an autoimmune disease in which the body's immune system becomes overactive, mistakes its own cells as foreign, and starts causing damage through inflammation. But these foamy microglia suggest there's also more to the story.

"We found that patients with large numbers of these foamy microglia had a more severe disease course more frequently," says molecular physiologist Daan van der Vliet, from Leiden University in the Netherlands.

"It does not appear to be simply about the inflammatory response alone."

The team analyzed post-mortem brain tissue from 28 people with secondary progressive MS, where the disease has progressed to the point where cognitive and physical function are declining.

This tissue was compared against samples from 10 donated brains from people without the disease.

Using a combination of profiling techniques, the researcher created a map of proteins, fats, and active genes for the brain regions affected by MS lesions.

These lesions form when the fatty, protective coating around nerve fibers, known as myelin, is attacked by immune cells that have become too aggressive.

Not only was there a link between more foamy microglia and MS progression, but the researchers also found that the microglia were changing the mode of inflammation around the lesions – they had a different molecular signature in terms of proteins and enzymes.

The researchers suggest that as microglia arrive to try and repair the damage done to neurons, they get clogged up with fats (beginning with myelin) and become overwhelmed, which in turn, makes the inflammation worse.

"These cells are probably trying to do something good: clearing up damage," says van der Vliet.

"But they become overloaded, so to speak. As a result, they can no longer effectively contribute to repair."

The researchers also used a mouse model of MS, blocking one of the enzymes most active in foamy microglia. Tissue healing improved in these mice, further emphasizing the connection between these immune cells and worse MS progression.

We're still in the early stages of this research, and clinical trials with MS patients will be needed to see if the foamy microglia link holds up.

Researchers will also need to look at how these lesions that aren't repaired continue to develop over time.

However, these are promising findings in terms of figuring out why some people with MS live relatively normal lives for decades, while others become paralyzed sooner or develop more severe symptoms at a young age.

The study team is hopeful that the findings could help develop new MS treatments that target fat metabolism in cells.

There's also the potential, along with other lines of research, to identify more severe cases of MS at an earlier stage.

The researchers found signs of fats associated with foamy microglia floating around in cerebrospinal fluid, which they say could be measured as a marker of the disease.

Related: Scientists Identify Specific Bacteria Linked to Multiple Sclerosis

"That opens the possibility of developing biomarkers in the future that could help doctors identify earlier which patients are at risk of rapid decline – and which treatment would suit them best," says van der Vliet.

The research has been published in Nature Neuroscience.

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