Rutgers University – Alzheimer’s may be linked to defective brain cells spreading disease

Rutgers scientists say neurodegenerative diseases like Alzheimer’s and Parkinson’s may be linked to defective brain cells disposing toxic proteins that make neighboring cells sick

In a study published in Nature, Monica Driscoll, distinguished professor of molecular biology and biochemistry, School of Arts and Sciences, and her team, found that while healthy neurons should be able to sort out and and rid brain cells of toxic proteins and damaged cell structures without causing problems, laboratory findings indicate that it does not always occur.

These findings, Driscoll said, could have major implications for neurological disease in humans and possibly be the way that disease can spread in the brain.

“Normally the process of throwing out this trash would be a good thing,” said Driscoll. “But we think with neurodegenerative diseases like Alzheimer’s and Parkinson’s there might be a mismanagement of this very important process that is supposed to protect neurons but, instead, is doing harm to neighbor cells.”

Driscoll said scientists have understood how the process of eliminating toxic cellular substances works internally within the cell, comparing it to a garbage disposal getting rid of waste, but they did not know how cells released the garbage externally.

“What we found out could be compared to a person collecting trash and putting it outside for garbage day,” said Driscoll. “They actively select and sort the trash from the good stuff, but if it’s not picked up, the garbage can cause real problems.”

Working with the transparent roundworm, known as the C. elegans, which are similar in molecular form, function and genetics to those of humans, Driscoll and her team discovered that the worms — which have a lifespan of about three weeks — had an external garbage removal mechanism and were disposing these toxic proteins outside the cell as well.

Ilija Melentijevic, a graduate student in Driscoll’s laboratory and the lead author of the study, realized what was occurring when he observed a small cloud-like, bright blob forming outside of the cell in some of the worms. Over two years, he counted and monitored their production and degradation in single still images until finally he caught one in mid-formation.

“They were very dynamic,” said Melentijevic, an undergraduate student at the time who spent three nights in the lab taking photos of the process viewed through a microscope every 15 minutes. “You couldn’t see them often, and when they did occur, they were gone the next day.”

Research using roundworms has provided scientists with important information on aging, which would be difficult to conduct in people and other organisms that have long life spans.

In the newly published study, the Rutgers team found that roundworms engineered to produce human disease proteins associated with Huntington’s disease and Alzheimer’s, threw out more trash consisting of these neurodegenerative toxic materials.

While neighboring cells degraded some of the material, more distant cells scavenged other portions of the diseased proteins.

“These finding are significant,” said Driscoll. The work in the little worm may open the door to much needed approaches to addressing neurodegeneration and diseases like Alzheimer’s and Parkinson’s.”

Story Source:

Materials provided by Rutgers University. Original written by Robin Lally. Note: Content may be edited for style and length.

Journal Reference:

  1. Ilija Melentijevic, Marton L. Toth, Meghan L. Arnold, Ryan J. Guasp, Girish Harinath, Ken C. Nguyen, Daniel Taub, J. Alex Parker, Christian Neri, Christopher V. Gabel, David H. Hall, Monica Driscoll. C. elegans neurons jettison protein aggregates and mitochondria under neurotoxic stress. Nature, 2017; DOI: 10.1038/nature21362

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Rutgers University. “Alzheimer’s may be linked to defective brain cells spreading disease: Study finds toxic proteins doing harm to neighboring neurons.” ScienceDaily. ScienceDaily, 10 February 2017. <>.

Identifying the ‘Culprit’ (molecule) for the Cause of Alzheimer’s: A ‘Big Bang’ Research Breakthrough at UT Southwestern O’Donnell Brain Institute + Video

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It’s being called the “big bang” breakthrough in Alzheimer’s research. Doctors at UT Southwestern’s O’Donnell Brain Institute have detected what they believe are changes in a single molecule that could act as the starting point for the deadly, memory-stealing disease.

Scientists are fairly certain that a molecule called “tau” is the culprit.

Alzheimer’s is characterized by clumps of tangled protein in the brain. According to the Alzheimer’s Association, one in three seniors will die of the disease — and that’s more than breast and prostate cancer combined.

Ultimately, researchers hope that warning signals for the disease can be effectively detected and therefore prevented with something as simple as a vaccine or pill.

“I anticipate a day when we will think about these diseases like Alzheimer’s and Parkinson’s as problems that only people who don’t get medical care develop,” said Dr. Diamond.

Researchers know that there is much work ahead. It could be several years before the discovery is ready for human clinical trials. Until then, supporters say it’s critical for lawmakers to fund research at all levels.UTSW II luo-chen

Patients can also get involved in local studies so doctors can learn as much as they can from seniors as they age. And while the advances won’t happen overnight, doctors say the overriding message for the community in the discovery is that there is hope.

“There’s tremendous hope!” said Dr. Diamond. “We are actually super excited in our field. When I look at the future, I see many, many opportunities for good shots on goal.”

And if he’s right, the discovery could be a life-changing win for the world.

Watch the Video


New Simple Blood Test can Detect Alzheimer’s 30 Years in Advance + Can Also Detect 8 Cancers: Videos

New Simple Blood Test can Detect Alzheimer’s 30 Years in Advance + Can Also Detect 8 Cancers


Watch the Videos Below

Detecting Alzheimer’s 30 Years in Advance

8 Cancers Detected with ONE Simple Blood Test

Molecular Inhibitor Breaks Cycle that leads to Alzheimer’s

vnDpjc0OLw.JPGA molecule that can block the progress of Alzheimer’s disease at a crucial stage in its development has been identified by researchers in a new study, raising the prospect that more such molecules may now be found.

The report shows that a molecular chaperone, a type of molecule that occurs naturally in humans, can play the role of an “inhibitor” part-way through the molecular process that is thought to cause Alzheimer’s, breaking the cycle of events that scientists believe leads to the disease.

Specifically, the molecule sticks to threads made up of malfunctioning proteins, called amyloid fibrils, which are the hallmark of the disease. By doing so, it stops these threads from coming into contact with other proteins, thereby helping to avoid the formation of highly toxic clusters that enable the condition to proliferate in the brain.

This step—where fibrils made up of malfunctioning proteins assist in the formation of toxic clusters—is considered to be one of the most critical stages in the development of Alzheimer’s in sufferers. By finding a molecule that prevents it from occurring, scientists have moved closer to identifying a substance that could eventually be used to treat the disease. The discovery was made possible by an overall strategy that could now be applied to find other molecules with similar capabilities, extending the range of options for future drug development.

The research was carried out by an international team comprising academics from the Dept. of Chemistry at the Univ. of Cambridge, the Karolinska Institute in Stockholm, Lund Univ., the Swedish Univ. of Agricultural Sciences and Tallinn Univ. Their findings are reported in Nature Structural & Molecular Biology.

Dr. Samuel Cohen, a Research Fellow at St John’s College, Cambridge, and a lead author of the report, said: “A great deal of work in this field has gone into understanding which microscopic processes are important in the development of Alzheimer’s disease; now we are now starting to reap the rewards of this hard work. Our study shows, for the first time, one of these critical processes being specifically inhibited, and reveals that by doing so we can prevent the toxic effects of protein aggregation that are associated with this terrible condition.”

Alzheimer’s disease is one of a number of conditions caused by naturally occurring proteins molecules folding into the wrong shape and then sticking together—or nucleating—with other proteins to create thin filamentous structures called amyloid fibrils. Proteins perform important functions in the body by folding into a particular shape, but sometimes they can misfold, potentially kick-starting this deadly process.

Recent research, much of it by the academics behind the latest study, had however suggested a second critical step in the disease’s development. After amyloid fibrils first form from misfolded proteins, they help other proteins which come into contact with them to misfold and form small clusters, called oligomers. These oligomers are highly toxic to nerve cells and are now thought to be responsible for the devastating effects of Alzheimer’s disease.

This second stage, known as secondary nucleation, sets off a chain reaction which creates many more toxic oligomers, and ultimately amyloid fibrils, generating the toxic effects that eventually manifest themselves as Alzheimer’s. Without the secondary nucleation process, single molecules would have to misfold and form toxic clusters unaided, which is a much slower and far less devastating process.

By studying the molecular processes by which each of these steps takes effect, the research team assembled a wealth of data that enabled them to model not only what happens during the progression of Alzheimer’s disease, but also what might happen if one stage in the process was somehow switched off.

“We had reached a stage where we knew what the data should look like if we inhibited any given step in the process, including secondary nucleation,” Cohen said. “Working closely with our collaborators in Sweden—who had developed groundbreaking experimental methods to monitor the process—we were able to identify a molecule that produced exactly the results that we were hoping to see in experiments.”

The results indicated that the molecule, Brichos, effectively inhibits secondary nucleation. Typically, Brichos functions as a “molecular chaperone” in humans; a term given to “housekeeping” molecules that help proteins to avoid misfolding and aggregation. Lab tests, however, revealed that when this molecular chaperone encounters an amyloid fibril, it binds itself to catalytic sites on its surface. This essentially forms a coating that prevents the fibrils from assisting other proteins in misfolding and nucleating into toxic oligomers.

The research team then carried out further tests in which living mouse brain tissue was exposed to amyloid-beta, the specific protein that forms the amyloid fibrils in Alzheimer’s disease. Allowing the amyloid-beta to misfold and form amyloid increased toxicity in the tissue significantly but, in the presence of the molecular chaperone, amyloid fibrils still formed but the toxicity did not develop in the brain tissue, confirming that the molecule that the team had identified had suppressed the chain reaction from secondary nucleation that feeds the catastrophic production of oligomers leading to Alzheimer’s disease.

By modelling what might happen if secondary nucleation is switched off and then finding a molecule that performs that function, the research team suggest that they have discovered a strategy that may lead to the discovery of many similar molecules that could have a similar effect.

“It may not actually be too difficult to find other molecules that do this, it’s just that it hasn’t been clear what to look for until recently,” Cohen said. “It’s striking that nature—through molecular chaperones—has evolved a similar approach to our own by focusing on very specifically inhibiting the key steps leading to Alzheimer’s. A good tactic now is to search for other molecules that have this same highly targeted effect and to see if these can be used as the starting point for developing a future therapy.”

Source: Univ. of Cambridge