BU researchers define possible molecular pathway for neurodegeneration in prion diseases

BU researchers define possible molecular pathway for neurodegeneration in prion diseases

https://www.eurekalert.org/pub_releases/2018-09/buso-brd092118.php

I wonder about prion diseases because I watched my grandfather degenerate from Alzheimers, and carried my suicidal grandmother into the Barrie, Ontario (that’s in Canada) hospital when I was 20 (that’s her, right, when I was a kid)

It sucked, and has scared me for 35 years.

But after years of therapy, I may be learning to deal with it.

My first book in 1997 was called Mad Cows and Mothers Milk for a reason.

A very personal reason.

A new study has shed light on the mechanisms underlying the progression of prion diseases and identified a potential target for treatment.

Prion diseases are a group of fatal neurological disorders that includes Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (“mad cow disease”). They are caused by the spread of “prions”, which are altered forms of normal cellular proteins. These abnormal molecules then interact with normal proteins to promote misfolding. While we understand that this process of converting normal to abnormal protein is what causes the symptoms of prion disease (including rapidly progressive dementia, seizures and personality changes), the exact mechanism of damage to the neuronal connections in the brain and spinal cord has been poorly understood.

Researchers from Boston University School of Medicine (BUSM) used a method they previously described for culturing nerve cells from the hippocampal region of the brain, and then exposing them to prions, to illustrate the damage to nerve cell connections usually seen in these diseases. They then added a number of different chemical compounds with known inhibitory effects on cellular responses to stressful stimuli, with the objective of identifying which pathways may be involved.

They found that inhibition of p38 MAPKα (an enzyme that typically responds to stress, such as ultraviolet radiation and heat shock) prevented injury to nerve connections and promoted recovery from the initial damage. Hippocampal nerve cells that had a mutation preventing normal function of p38 MAPKα were also protected, seeming to confirm the role the enzyme plays in this disease process.

David. A. Harris, MD, PhD, professor and chair of the Department of Biochemistry at Boston University School of Medicine and corresponding author of the study, sees these findings as a major breakthrough in trying to understand and treat these diseases. “Our results provide new insights into the pathogenesis of prion diseases, they uncover new drug targets for treating these diseases, and they allow us to compare prion diseases to other, more common neurodegenerative disorders like Alzheimer’s disease.”

These findings appear online in PLOS Pathogens.

 

My super-smart partner and I meet: Prion disease in Algerian camels

Amy says I shouldn’t cut-and-paste so much and that I’m better when I just write my own stuff.

Howard Stern’s wife said that to him, at least according to the movie version in Private Parts, 1997, but I counter with I only cut-and-paste the really interesting stuff.

Algeria, French and prions, we’re in a zone.

Everyone else is recall.net, where the copy is provided by 100K-a-year hacks who write and vomit press releases.

Journalism used to be a viable activity.

No worries, story-telling about the Tom-Wolfe-styled-vanities of the food safety privileged retain currency. And those stories are what I have been working on,

I’ll go with a Paul Giamatti,-style, who I am enjoying in Billions and was great in John Adams, Cinderella Man, American Splendor, and so on.

Everyone needs a Paul.

Or an Amy.

Her accomplishments over the seven years since we moved to Australia, including caretaking me and Sorenne, have been extraordinary.

Much love.

Prion disease in Dromedary camels, Algeria

6 June 2018

Emerging Infectious Diseases Vol 24, no 6

Baaissa Babelhadj, Michele Angelo Di Bari, Laura Pirisinu, Barbara Chiappini, Semir Bechir Suheil Gaouar, Geraldina Riccardi, Stefano Marcon, Umberto Agrimi, Romolo Nonno, and Gabriele Vaccari

https://wwwnc.cdc.gov/eid/article/24/6/17-2007_article

Prions cause fatal and transmissible neurodegenerative diseases, including Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (BSE).

After the BSE epidemic, and the associated human infections, began in 1996 in the United Kingdom, general concerns have been raised about animal prions.

We detected a prion disease in dromedary camels (Camelus dromedarius) in Algeria. Symptoms suggesting prion disease occurred in 3.1% of dromedaries brought for slaughter to Ouargla abattoir in 2015–2016. We confirmed diagnosis by detecting pathognomonic neurodegeneration and disease-specific prion protein (PrPSc) in brain tissues from 3 symptomatic animals.

Prion detection in lymphoid tissues is suggestive of the infectious nature of the disease. PrPSc biochemical characterization showed differences with BSE and scrapie.

Our identification of this prion disease in a geographically widespread livestock species requires urgent enforcement of surveillance and assessment of the potential risks to human and animal health.

 

 

Wow: Grass plants can transport infectious prions

Grass plants can bind, uptake and transport infectious prions, according to researchers at The University of Texas Health Science Center at Houston (UTHealth). The research was published online in the latest issue of Cell Reports.

prion.plants.may.15Prions are the protein-based infectious agents responsible for a group of diseases called transmissible spongiform encephalopathy, which includes bovine spongiform encephalopathy (mad cow disease) in cattle, scrapie in sheep, variant Creutzfeldt-Jakob disease in humans and chronic wasting disease (CWD) in deer, elk and moose. All are fatal brain diseases with incubation periods that last years.

CWD, first diagnosed in mule deer in Colorado in the late 1960s, has spread across the country into 22 states, according to the Centers for Disease Control and Prevention (CDC), including the counties of El Paso and Hudspeth in Texas. In northeastern Colorado and southeastern Wyoming, the disease is endemic. Soto’s team sought to find out why.

“There is no proof of transmission from wild animals and plants to humans,” said lead author Claudio Soto, Ph.D., professor of neurology at UTHealth Medical School and director of the UTHealth George and Cynthia W. Mitchell Center for Alzheimer’s Disease and Other Brain Related Illnesses. “But it’s a possibility that needs to be explored and people need to be aware of it. Prions have a long incubation period.”

Soto’s team analyzed the retention of infectious prion protein and infectivity in wheat grass roots and leaves incubated with prion-contaminated brain material and discovered that even highly diluted amounts can bind to the roots and leaves. When the wheat grass was consumed by hamsters, the animals were infected with the disease. The team also learned that infectious prion proteins could be detected in plants exposed to urine and feces from prion-infected hamsters and deer.

Researchers also found that plants can uptake prions from contaminated soil and transport them to different parts of the plant, which can act as a carrier of infectivity. This suggests that plants may play an important role in environmental prion contamination and the horizontal transmission of the disease.

To minimize the risk of exposure to CWD, the CDC recommends that people avoid eating meat from deer and elk that look sick or test positive for CWD. Hunters who field-dress deer in an affected area should wear gloves and minimize handling of the brain and spinal cord tissues.

“This research was done in experimental conditions in the lab,” Soto said of the next step. “We’re moving the research into environmental contamination now.”

First author of the paper, “Grass Plants Bind, Retain, Uptake and Transport Infectious Prions,” is post-doctoral researcher Sandra Pritzkow, Ph.D. Co-authors from UTHealth are Rodrigo Morales, Ph.D.; Fabio Moda, Ph.D.; and Uffaf Khan. Co-authors from the Prion Research Center at the College of Veterinary Medicine and Biomedical Sciences, Colorado State University, are Glenn C. Telling, Ph.D.; and Edward Hoover, D.V.M., Ph.D.

Stanley Prusiner: a victory lap for a heretical neurologist

Abigail Zuger of the New York Times writes that sweet revenge comes in many delectable forms, among them the receipt of accolades for work long scorned. And then to get to tell the whole story at length and without a single interruption — small wonder that the Nobel laureate Dr. Stanley B. Prusiner, a renowned neurologist at the University of California, San Francisco, writes with a cheerful bounce. Once disparaged, his scientific work is now hailed as visionary, and his memoir takes the reader on a leisurely and immensely readable victory lap from then to now.

PRUSINERIn the process, two stories unfold. The first is the progress of Dr. Prusiner’s thinking on the transmissible proteins he named prions (PREE-ons) in 1982, starting with his first experiments on an obscure disease of sheep and ending with the most recent work linking prions to an array of human neurological catastrophes, including Alzheimer’s disease. The science is convoluted, like the proteins, and for the uninitiated the best way to achieve a rudimentary grasp of the subject is to hear it the way Dr. Prusiner tells it, from the very beginning.

But a parallel narrative turns out to be equally fascinating: perhaps not since James D. Watson’s 1968 memoir “The Double Helix“ has the down and dirty business of world-class science been given such an airing. Dr. Watson raised eyebrows with his gossipy account of the serious task of unraveling the genetic code — and he was working in genteel postwar Britain at the time, with experimental science still at least in theory a gentleman’s game. That illusion is long gone: The stakes are considerably higher now, the competition fierce, the pace frantic, and Dr. Prusiner, 71, revisits quite a few of the battles that punctuated his long research career.