Latest Research Suggests Alzheimer’s Disease Is In Our Food


Genetic mutation blocks prion disease


Unknown mechanism helped some people in Papua New Guinea escape historic, deadly outbreak.

A genetic variant protected some practitioners of cannibalism from prion disease.

Scientists who study a rare brain disease that once devastated entire communities in Papua New Guinea have described a genetic variant that appears to stop misfolded proteins known as prions from propagating in the brain1.

Kuru was first observed in the mid-twentieth century among the Fore people of Papua New Guinea. At its peak in the late 1950s, the disease killed up to 2% of the group’s population each year. Scientists later traced the illness to ritual cannibalism2, in which tribe members ate the brains and nervous systems of their dead. The outbreak probably began when a Fore person consumed body parts from someone who had sporadic Creutzfeldt-Jakob disease (CJD), a prion disease that spontaneously strikes about one person in a million each year.

Scientists have noted previously that some people seem less susceptible to prion diseases if they have an amino-acid substitution in a particular region of the prion protein — codon 1293. And in 2009, a team led by John Collinge — a prion researcher at University College London who is also the lead author of the most recent analysis — found another protective mutation among the Fore, in codon 1274.

The group’s latest work, reported on 10 June in Nature1, shows that the amino-acid change that occurs at this codon, replacing a glycine with a valine, has a different and more powerful effect than the substitution at codon 129. The codon 129 variant confers some protection against prion disease only when it is present on one of the two copies of the gene that encodes the protein. But transgenic mice with the codon-127 mutation were completely resistant to kuru and CJD regardless of whether they bore one or two copies of it.

The researchers say that the mutation in codon 127 appears to confer protection by preventing prion proteins from becoming misshapen.

“It is a surprise,” says Eric Minikel, a prion researcher at the Broad Institute in Cambridge, Massachusetts. “This was a story I didn’t expect to have another chapter.”

Collinge and his colleagues are now continuing their work, to figure out the mutant protein’s structure and how it shields against illness.

Plants may form memories using mad cow disease proteins.


Prions – those infamous proteins linked to mad cow disease – may be responsible for memory in plants.

The yellow blooms of a flowering mustard plant

The proteins may help plants change their activity based on past events, helping them decide when to flower, for instance.

That plants have memory is well known. For instance, certain plants flower after a prolonged exposure to cold. But if the conditions are not right following the cold, the plant will delay flowering until temperature and light are just right. This suggests that plants “remember” the exposure to cold.

You can even take tissue from such plants and grow a new plant, and it, too, will remember the encounter with the cold, and flower accordingly. The biological state is somehow perpetuated in both the original and new plants.

“Plants have lots of states that they self-perpetuate,” says Susan Lindquist of the Massachusetts Institute of Technology. “They have memory in some ways.”

A prion protein can fold in two ways: it has a normal form and a prion form. Once it folds into a prion, it can then cause similar proteins to change their folding, turning them into prions too.

Lindquist’s team already knew that yeasts use prions as a form of memory, and suspected that plants might too. Unlike in Creuzfeldt-Jakob disease, the human equivalent of BSE or  “mad cow disease”, where prions multiply in the human brain with terrible consequences, prions in yeast are beneficial. They can help the organism use different nutrients and grow in new places.

Crucially, this ability persists over generations. “It could be state that only lasts for 50 generations, or it could last for thousands and thousands of generations,” says Lindquist.

The team applied techniques developed for finding prions in yeast to Arabidopsis thaliana, a flowering mustard plant. Their method involves using specialised algorithms to search the full complement of proteins expressed by the plant.

The researchers found four proteins involved in flowering that had portions that resembled prion-specific sequences in yeast.

Next, the team replaced the prions in yeast cells with the prion-like protein sequences from Arabidopsis, and confirmed that the three of the four plant protein fragments did indeed behave like prions.

This is the first time a prion-like protein sequence has been found in plants. “We don’t know what it’s actually doing in the plant, so we are trying to be cautious,” says Lindquist. “That’s why we call it prion-like.”

The finding is “very significant”, says Frantisek Baluska at the University of Bonn, Germany, an expert on plant intelligence. “In fact, I was expecting the discovery of prions in plants.”

“Prions, we think, are responsible for some really broad, really interesting biology,” says Lindquist. “We have only seen the tip of the iceberg so far.”

Yeast are first cells known to cure themselves of prions


Yeast cells can sometimes reverse the protein misfolding and clumping associated with diseases such as Alzheimer’s, according to new research from the University of Arizona.

The new finding contradicts the idea that once prion proteins have changed into the shape that aggregates, the change is irreversible.

“It’s believed that when these aggregates arise that cannot get rid of them,” said Tricia Serio, UA professor and head of the department of molecular and cellular biology. “We’ve shown that’s not the case. Cells can clear themselves of these aggregates.”

Prions are proteins that change into a shape that triggers their neighbors to change, also. In that new form, the proteins cluster. The aggregates, called amyloids, are associated with diseases including Alzheimer’s, Huntington’s and Parkinson’s.

“The is kind of like Dr. Jekyll and Mr. Hyde,” said Serio, senior author of the paper published today in the open-access journal eLife. “When you get Hyde, all the prion that gets made after that is folded in that bad way.”

For yeast, having clumps of amyloid is not fatal. Serio and her students exposed amyloid-containing cells of baker’s yeast to 104 F (40 C), a temperature that would be a high fever in a human. When exposed to that environment, the cells activated a stress response that changed the clumping proteins back to the no-clumping shape.

The finding suggests artificially inducing stress responses may one day help develop treatments for diseases associated with misfolded prion proteins, Serio said.

“People are trying to develop therapeutics that will artificially induce stress responses,” she said. “Our work serves as a proof of principal that it’s a fruitful path to follow.”

First author on the paper “Spatial quality control bypasses cell-based limitations on proteostasis to promote prion curing” is Serio’s former graduate student Courtney Klaips, now at the Max Planck Institute for Biochemistry in Munich. The other authors are Serio’s students Megan Hochstrasser, now at the University of California, Berkeley, and Christine Langlois of Brown University.

These yeast cells contain a prion protein that can change shape from a non-clumping form to one that aggregates into clumps called amyloids. Proteins in these cells have the non-clumping shape and are tagged with a marker that fluoresces green under UV light. Credit: Serio laboratory/ UA molecular and cellular biology

To accomplish their jobs inside cells, proteins must fold into specific shapes. Cells have quality-control mechanisms that usually keep proteins from misfolding. However, under some environmental stresses, those mechanisms break down and proteins do misfold, sometimes forming amyloids.

Cells respond to environmental stress by making specific proteins, known as heat-shock proteins, which are known to help prevent .

Serio and her students wanted to know whether particular heat-shock proteins could make amyloids revert to the normal shape. To that end, the team studied that seemed unable to clear themselves of the amyloid form of the prion protein Sup35.

The researchers were testing one heat-shock protein at a time in an attempt to figure out which particular proteins were needed to clear the amyloids. However, the results weren’t making sense, she said.

So she and Klaips decided to stress yeast cells by exposing them to a range of elevated temperatures – as much as 104 F (40 C) – and let the cells do what comes naturally.

As a result, the cells made a battery of heat-shock proteins. The researchers found at one specific stage of the cell’s reproductive cycle, the yeast could turn aggregates of Sup35 back into the non-clumping form of the protein.

Yeast cells reproduce by budding. The mother cell partitions off a bit of itself into a much smaller daughter cell, which separates and then grows up.

The researchers found in the heat-stressed yeast, just when the daughter was being formed, the mother cell retained most of the heat-shock proteins called chaperones, especially Hsp-104. As a result, the mother had a particularly high concentration of Hsp-104 because little of the protein was shared with the daughter.

The fluorescent green chunks in these yeast cells are prion proteins that have assumed the shape that aggregates into clumps called amyloids. The prion proteins in these cells are tagged with a marker that fluoresces green under UV light. Credit: Serio laboratory/ UA molecular and cellular biology

The mother cells ended up “curing” themselves of the Sup35 amyloid, although the daughters did not. The degree of curing was correlated with the concentration of Hsp-104 in the cell, and the higher the temperature the more Hsp-104 the cells had.

The Hsp-104 takes the protein in the amyloid and refolds it, Serio said. But she and her colleagues found that just inducing high levels of Hsp-104 in cells by itself does not change the  back to the non-clumping form.

“Clearly the heat-shock proteins are collaborating in some way that we don’t understand,” she said.

Having the amyloid-forming version of the protein is not automatically bad, she said. It may be that shape is good under some environmental conditions, whereas the non-aggregating form is good under others.

Even in humans, amyloid forms of a protein can be helpful, she said. Amyloid proteins are associated with skin pigmentation and with hormone storage.

To clear the amyloid from yeast cells, these experiments triggered cells to make many different heat-shock proteins.

Serio now wants to figure out the minimal system necessary to clear amyloids from a cell. Knowing that may help the development of drug therapies for amyloid-related human diseases, she said.

Prions can trigger ‘stuck’ wine fermentations, researchers find


A chronic problem in winemaking is “stuck fermentation,” when yeast that should be busily converting grape sugar into alcohol and carbon dioxide prematurely shuts down, leaving the remaining sugar to instead be consumed by bacteria that can spoil the wine.

A team of researchers including UC Davis geneticist Linda Bisson has discovered a biochemical communication system behind this problem. Working through a prion—an abnormally shaped protein that can reproduce itself—the system enables in fermenting wine to switch yeast from sugar to other food sources without altering the yeast’s DNA.

“The discovery of this process really gives us a clue to how stuck fermentations can be avoided,” said Bisson, a professor in the Department of Viticulture and Enology. “Our goal now is to find yeast strains that essentially ignore the signal initiated by the bacteria and do not form the prion, but instead power on through the fermentation.”

She suggests that the discovery of this biochemical mechanism, reported Aug. 28 in the journal Cell, may also have implications for better understanding metabolic diseases, such as Type 2 diabetes, in humans.

Bacteria, yeast and fermentation:

Biologists have known for years that an ancient biological circuit, based in the membranes of , blocks yeast from using other carbon sources when the sugar glucose is present.

This circuit, known as “glucose repression,” is especially strong in the yeast species Saccharomyces cerevisiae, enabling people to use that yeast for practical fermentation processes in winemaking, brewing and bread making, because it causes such efficient processing of sugar.

Prions play key role:

In this study, the researchers found that the glucose repression circuit is sometimes interrupted when bacteria jump-start the replication of the prions in membranes of yeast cells. The interference of the prions causes the yeast to process carbon sources other than glucose and become less effective in metabolizing sugar, dramatically slowing down the fermentation until it, in effect, becomes “stuck.”

“This type of prion-based inheritance is useful to organisms when they need to adapt to environmental conditions but not necessarily permanently,” Bisson said. “In this case, the heritable changes triggered by the prions enable the yeast to also change back to their initial mode of operation if environmental conditions should change again.”

The researchers demonstrated in this study that the process leading to a stuck fermentation benefits both the bacteria and the yeast. As metabolism slows down, conditions in the fermenting wine become more conducive to bacterial growth, and the yeast benefit by gaining the ability to metabolize not only glucose but also other carbon sources as well—maintaining and extending their lifespan.

Solutions for winemakers:

Now that this communication mechanism between the bacteria and yeast is more clearly understood, winemakers should be better able to avoid stuck fermentations.

“Winemakers may want to alter the levels of sulfur dioxide used when pressing or crushing the grapes, in order to knock out bacteria that can trigger the processes that we now know can lead to a stuck fermentation,” Bisson said. “They also can be careful about blending grapes from vineyards known to have certain bacterial strains or they could add yeast strains that have the ability to overpower these vineyard bacteria.”

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