SharecloseShare pageCopy linkAbout sharingThere is no “additional DNA damage” in children born to parents who were exposed to radiation from the Chernobyl explosion before they were conceived.This is according to the first study to screen the genes of children whose parents were enlisted to help in the clean-up after the nuclear accident. Participants, all conceived after the disaster and born between 1987 and 2002, had their whole genomes screened.The study found no mutations that were associated with a parent’s exposure. The findings are published in the journal Science. Chernobyl: The end of a three-decade experimentChernobyl vodka made in exclusion zoneimage copyrightG LaptevProf Gerry Thomas, from Imperial College London, has spent decades studying the biology of cancer, particularly tumours that are linked to damage from radiation. She explained that this new study was the first to demonstrate that “even when people were exposed to relatively high doses of radiation – when compared to background radiation – it had no effect on their future children”. The new study was led by Prof Meredith Yeager, at the US National Cancer Institute (NCI), in Maryland. It focused on the children of workers who were enlisted to help clean up the highly-contaminated zone around the nuclear power plant, and the children of evacuees from the abandoned town of Pripyat, and other settlements within the 70km zone around it.One of the lead researchers, Dr Stephen Chanock, also from the NCI, explained that the research team recruited whole families, so the scientists could compare the DNA of a mother, a father and a child. “Here we’re not looking at what happened to those children who were [in the womb] at the time of the accident; we’re looking at something called de novo mutations.”These are new mutations in DNA – they occur randomly in an egg or sperm cell. Depending on where in the genetic blueprint of a baby a mutation arises, it could have no impact at all, or could be the cause of a genetic disease. “There are about 50-100 of these mutations every generation – and they’re random,” explained Dr Chanock. “In some ways, they’re the building blocks of evolution. This is how new changes are introduced into a population one birth at a time. “We looked at the mothers’ and the fathers’ genomes and then at the child. And we spent an extra nine months looking for any signal – in the number of these mutations – that was associated with a parents’ radiation exposure. We couldn’t find anything.”This means, the scientists say, that the effect of radiation on a parent’s body has no impact on the children they conceive in the future. “There are a lot of people who were scared to have children after the atomic bombs [in Nagasaki and Hiroshima],” Prof Thomas told BBC News. “And people who were scared to have children after the accident at Fukushima, because they thought their child would be affected by radiation they were exposed to.”It’s so sad. And if we can show that there’s no effect, hopefully we can alleviate that fear.”Prof Thomas was not involved in the genome study. She and her colleagues have carried out another piece of research on the cancers that were linked to Chernobyl. They studied thyroid cancer, because the nuclear accident is known to have caused about 5,000 cases of that specific cancer, the vast majority of which were treated and cured.The authorities at the time of the accident failed to prevent contaminated milk from being sold in the region; many who were children at the time drank it, receiving large doses of radioactive iodine – one of the contaminants blasted out of the damaged reactor.”Essentially, we found that there is no difference between thyroid cancers caused by Chernobyl radiation and any other thyroid cancers,” Prof Thomas explained. “So there’s no ‘demon tumour’ that comes out of Chernobyl that we won’t be able to treat – we can just treat in exactly the same way as we treat other cases.” Follow Victoria on Twitter

Mice with symptoms that mimic Bardet-Biedl Syndrome (BBS) have difficulty with learning and generating new neurons in the hippocampus. However, according to a new study by Thomas Pak, Calvin Carter, and Val Sheffield of the University of Iowa, published April 22nd in the journal PLOS Genetics, these mental defects can be successfully treated with lithium.
BBS is a rare genetic disorder that causes intellectual disability, vision loss and obesity, and sometimes kidney problems and extra fingers and toes. It is one of several ciliopathies, which are diseases that stem from defective cilia — tiny, finger-like projections on the surface of cells that play important roles in moving fluids, sensing the environment and signaling between cells. Pak, Carter, Sheffield and colleagues wanted to learn more about how ciliopathies cause intellectual disability, so they studied a type of mouse with the same symptoms as people with BBS.
In the new study, the researchers showed that normal mice could quickly be trained to associate a specific environment to a fearful event, but the BBS mice had a harder time with fear memory. Further investigation showed that these learning problems come from an inability to make new neurons in the hippocampus. Treating the mice with lithium, however, increased cell production and improved their learning and memory.
Intellectual disability is the most common type of neurodevelopmental disorder, but few drugs are available to treat it. The new study suggests that lithium may be an effective treatment for the learning and memory defects caused by BBS, and the researchers suggest that further studies should be performed to test the use of this FDA-approved drug. The new findings also demonstrate a novel role for cilia in learning and memory in the brain, potentially improving our understanding of the mechanisms that cause intellectual disability.
Pak adds, “A mouse model of a cilia disease, Bardet-Biedl Syndrome, has impaired fear memory and hippocampal neurogenesis. In this mouse model, lithium treatment improves fear memory and hippocampal neurogenesis.”
Story Source:
Materials provided by PLOS. Note: Content may be edited for style and length.

In a worldwide study of 2,100 pregnant women, those who contracted COVID-19 during pregnancy were 20 times more likely to die than those who did not contract the virus.
UW Medicine and University of Oxford doctors led this first-of-its-kind study, published today in JAMA Pediatrics. The investigation involved more than 100 researchers and pregnant women from 43 maternity hospitals in 18 low-, middle- and high-income nations; 220 of the women received care in the United States, 40 at UW Medicine. The research was conducted between April and August of 2020.
The study is unique because each woman affected by COVID-19 was compared with two uninfected pregnant women who gave birth during the same span in the same hospital.
Aside from an increased risk of death, women and their newborns were also more likely to experience preterm birth, preeclampsia and admission to the ICU and/or intubation. Of the mothers who tested positive for the disease, 11.5% of their babies also tested positive, the study found.
Although other studies have looked at COVID-19’s effects on pregnant women, this is among the first study to have a concurrent control group with which to compare outcomes, said Dr. Michael Gravett, one of the study’s lead authors.
“The No. 1 takeaway from the research is that pregnant women are no more likely to get COVID-19, but if they get it, they are more likely to become very ill and more likely to require ICU care, ventilation, or experience preterm birth and preeclampsia,” he said. Gravett is a professor of obstetrics and gynecology at the University of Washington School of Medicine. Co-investigator Dr. Lavone Simmons is a UW acting assistant professor of OB-GYN.
One caveat, Gravett noted, was that women whose COVID-19 was asymptomatic or mild were not found to be at increased risk for ICU care, preterm birth or preeclampsia. About 40% of the women in this study were asymptomatic. Pregnant women who were obese or had hypertension or diabetes were at the greatest risk for severe disease, the findings showed.
Babies of the women infected with COVID-19 were more likely to be born preterm; but their infections were usually mild, the study found. Breastfeeding seemed not to be related to transmitting the disease. Delivery by Caesarean section, however, might be associated with an increased risk of having an infected newborn, the study found.
Gravett suggested that these and parallel research findings compelled U.S. states’ decisions to open vaccine eligibility to pregnant women — who were initially considered a population at low risk for severe COVID-19.
“I would highly recommend that all pregnant women receive the COVID-19 vaccines,” based on this research, he said.
The study demonstrates the importance of collecting large-scale, multinational data quickly during a health crisis, Gravett said. Researchers were able to complete the investigation and report findings in only nine months, using infrastructure already in place from the INTERGROWTH-21st Project, which emerged in 2012 to study fetal growth and neonatal outcomes.

In 1966, he found heat-resistant bacteria in a hot spring at Yellowstone National Park. That led to the development of the chemical process behind the test for Covid-19.Thomas Brock, a microbiologist, was driving west to a laboratory in Washington State in 1964 when he stopped off at Yellowstone National Park.“I’d never seen Yellowstone before,” he said in an interview in 2017. “I came in the south entrance, got out of my car, and there were all these thermal areas spreading out from the hot springs into the lake. I was stunned by the microbes that were living in the hot springs, and nobody seemed to know anything about them.”What fascinated him, on what would be the first of many trips to Yellowstone, were the blue-green algae living in a hot spring — proof that some life could tolerate temperatures above the boiling point of water.It was the beginning of research that led to a revolutionary find in 1966: a species of bacteria that he called Thermus aquaticus, which thrived at 70 degrees Celsius (158 degrees Fahrenheit) or more.The yellow bacteria — discovered by Dr. Brock and Hudson Freeze, his undergraduate assistant at Indiana University — survived because all their enzymes are stable at very high temperatures, including one, Taq polymerase, that replicates its own DNA and was essential to the invention of the process behind the gold standard in Covid-19 testing.Dr. Brock died on April 4 at his home in Madison, Wis. He was 94.His wife, Katherine (Middleton) Brock, known as Kathie, said the cause was complications of a fall.Thermus aquaticus was used in the 1980s by the biochemist Kary B. Mullis to help create the polymerase chain reaction, or PCR, which earned him a share of the 1993 Nobel Prize in Chemistry.Dr. Brock made his discovery after he became fascinated by the blue-green algae living in a hot spring. They offered proof that some life tolerated temperatures above the boiling point of water.Thomas Brock“I remember running into Mullis at a meeting,” Dr. Freeze, now the director of the human genetics program at Sanford-Burnham Prebys Medical Discovery Institute in San Diego, said in an interview. “And I said, ‘I’m the guy who found Thermus aquaticus with Tom Brock,’ and he said that he used the very strain that we isolated in Yellowstone.” (Dr. Brock had deposited cultures at the American Type Culture Collection in Gaithersburg, Md.)The PCR technology, which requires cycles of extreme heating and cooling, can multiply small segments of DNA millions or even billions of times in a short period. It has proved crucial in many ways, including the identification of DNA at a crime scene and, more recently, detecting whether someone has Covid-19.“PCR is fundamental to everything we do in molecular biology today,” said Yuka Manabe, a professor of medicine in the division of infectious diseases at the Johns Hopkins University School of Medicine. “Mullis couldn’t have done PCR without a rock-stable enzyme.”Thomas Dale Brock was born on Sept. 10, 1926, in Cleveland. His father, Thomas, an engineer who ran the boiler room at a hospital, died when Tom was 15, pushing him and his mother, Helen (Ringwald) Brock, a nurse, into poverty. Tom, an only child, took jobs in stores to help her.When he was a teenager, his interest in chemistry led him to set up a small laboratory with a friend in the loft of a barn behind his house in Chillicothe, Ohio, where he and his mother lived after his father’s death. They experimented there with explosives and toxic gas.After serving in the Navy’s electronics training program, Dr. Brock earned three degrees at Ohio State University: a bachelor’s in botany and a master’s and Ph.D. in mycology, the study of fungi.With faculty jobs in short supply, Dr. Brock spent five years as a research microbiologist at the Upjohn Company before he was hired as an assistant professor of biology at Western Reserve University (now Case Western Reserve University) in Cleveland. After two years, he became a postdoctoral fellow in the university’s medical school. In 1960, he joined the department of bacteriology at Indiana University, Bloomington, where he taught medical microbiology.When he arrived at Yellowstone, he did not have grandiose ambitions.A view of a Thermus aquaticus bacterium. It is able to survive hot temperatures because of an enzyme called Taq polymerase that protects it from heat.UW-Madison News & Public Affairs“I was just looking for a nice, simple ecosystem where I could study microbial ecology,” he said in an interview for the website of the University of Wisconsin, Madison, where he was a professor of natural sciences in the department of bacteriology from 1971 to 1990. “At higher temperatures, you don’t have the complications of having animals that eat all the microbes.”Stephen Zinder worked with Dr. Brock as a student from 1974 to 1977, a period that included Dr. Brock’s last summer of work at Yellowstone and his research into the ecology of Wisconsin’s lakes, including Lake Mendota in Madison.“He had an encyclopedic knowledge of microbiology and science in general,” said Dr. Zinder, now a professor of microbiology at Cornell University. “He was always learning and picking up new things.” He added, “I think his real ability was to see things simply and to figure out simple techniques to find out what the organisms were doing in their environment.”Dr. Brock wrote or edited numerous books, including “Milestones in Microbiology” (1961); “Biology of Microorganisms” (1970), now in its 16th edition; and “A Eutrophic Lake: Lake Mendota, Wisconsin” (1985).After retiring from the University of Wisconsin, Dr. Brock focused on ecological strategies to restore oak savanna, prairie and marshland on 140 acres that he and his wife had purchased in Black Earth, Wis., about 35 minutes from Madison.Dr. Brock in 2013 at the Pleasant Valley Conservancy in Black Earth, Wis. He and his wife, the microbiologist Katherine (Middleton) Brock, restored 140 acres of oak savanna, prairie and marshland there.Jeff Miller/UW-MadisonThe land, initially intended as a place for their two children to play, later became the Pleasant Valley Conservancy.“It was less expensive than land nearer Madison, and it turned out to be more interesting,” said Mrs. Brock, who is also a microbiologist.In addition to his wife, Dr. Brock is survived by their daughter, Emily Brock, and their son, Brian. His first marriage, to Mary Louise Louden, ended in divorceTo Dr. Brock, the discovery of Thermus aquaticus exemplified the benefits of being given the freedom to perform fundamental research without fixating on practical results.“It’s kind of an interesting story,” he told Wyoming Public Radio in 2020, “how research that was being done for just basic research, trying to find out what kind of weird critters might be living in boiling water in Yellowstone,” would eventually lead to “extremely widespread practical applications.”

In two landmark studies, researchers have used cutting-edge genomic tools to investigate the potential health effects of exposure to ionizing radiation, a known carcinogen, from the 1986 accident at the Chernobyl nuclear power plant in northern Ukraine. One study found no evidence that radiation exposure to parents resulted in new genetic changes being passed from parent to child. The second study documented the genetic changes in the tumors of people who developed thyroid cancer after being exposed as children or fetuses to the radiation released by the accident.
The findings, published around the 35th anniversary of the disaster, are from international teams of investigators led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health. The studies were published online in Science on April 22.
“Scientific questions about the effects of radiation on human health have been investigated since the atomic bombings of Hiroshima and Nagasaki and have been raised again by Chernobyl and by the nuclear accident that followed the tsunami in Fukushima, Japan,” said Stephen J. Chanock, M.D., director of NCI’s Division of Cancer Epidemiology and Genetics (DCEG). “In recent years, advances in DNA sequencing technology have enabled us to begin to address some of the important questions, in part through comprehensive genomic analyses carried out in well-designed epidemiological studies.”
The Chernobyl accident exposed millions of people in the surrounding region to radioactive contaminants. Studies have provided much of today’s knowledge about cancers caused by radiation exposures from nuclear power plant accidents. The new research builds on this foundation using next-generation DNA sequencing and other genomic characterization tools to analyze biospecimens from people in Ukraine who were affected by the disaster.
The first study investigated the long-standing question of whether radiation exposure results in genetic changes that can be passed from parent to offspring, as has been suggested by some studies in animals. To answer this question, Dr. Chanock and his colleagues analyzed the complete genomes of 130 people born between 1987 and 2002 and their 105 mother-father pairs.
One or both of the parents had been workers who helped clean up from the accident or had been evacuated because they lived in close proximity to the accident site. Each parent was evaluated for protracted exposure to ionizing radiation, which may have occurred through the consumption of contaminated milk (that is, milk from cows that grazed on pastures that had been contaminated by radioactive fallout). The mothers and fathers experienced a range of radiation doses.

For reasons not yet clear, pregnant women infected with the virus that causes COVID-19 are more likely to experience preterm births, pre-eclampsia, and other neonatal problems than non-infected women.
A team of Yale scientists decided to investigate whether the virus could be affecting placental tissue of infected expectant mothers. Their analysis found that while evidence of the virus in the placenta is rare, the placenta in infected mothers tended to exhibit a much higher level of immune system activity than those of non-infected pregnant women, they report April 22 in the journal Med.
“The good news is the placenta is mounting a robust defense against an infection that is far distant, in lungs or nasal tissue,” said Shelli Farhadian, assistant professor of internal medicine (infectious diseases) and neurology at Yale and co-corresponding author. “On the other hand, the high level of immune system activity might be leading to other deleterious effects on the pregnancy.”
The team headed by Farhadian and Akiko Iwasaki, the Waldemar Von Zedtwitz Professor of Immunobiology at Yale, analyzed blood and placental tissue in 39 infected and as well as COVID-free expectant mothers at different stages of pregnancy. While they found evidence of the virus in only two samples of placental tissue, they did find ACE2 receptors — which the SARS-CoV-2 virus uses to enter cells — in the placentas of most women during the first trimester of pregnancy. Those receptors had largely disappeared in healthy women at later stages of pregnancy.
“It is very important to closely monitor expectant mothers who become infected early in pregnancy,” Farhadian said.
Immune system activity in the placenta during infections like COVID-19 has not been extensively studied and it is not known whether other types of infections would behave similarly to SARS-CoV-2, she said.
Alice Lu-Culligan is lead author of the study, which was primarily funded by the National Institutes of Health and the Emergent Ventures Fund at the Mercatus Center at George Mason University.
Story Source:
Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

Not all cancerous tumors are created equal. Some tumors, known as “hot” tumors, show signs of inflammation, which means they are infiltrated with T cells working to fight the cancer. Those tumors are easier to treat, as immunotherapy drugs can then amp up the immune response.
“Cold” tumors, on the other hand, have no T-cell infiltration, which means the immune system is not stepping in to help. With these tumors, immunotherapy is of little use.
It’s the latter type of tumor that researchers Michael Knitz and radiation oncologist and University of Colorado Cancer Center member Sana Karam, MD, PhD, address in new research published this week in the Journal for ImmunoTherapy of Cancer. Working with mouse models in Karam’s specialty area of head and neck cancers, Knitz and Karam studied the role of T cells in tumor treatment.
“What we found is that the cells that normally tell the T cell, ‘Hey, here’s a tumor — come and attack it,’ are being silenced,” Karam says.
She and her team found that regulatory T cells (Tregs), a specialized T cell type that suppresses immune response, are essentially telling the T cells to stop fighting the cancer.
“Tregs normally serve as an important balance in a healthy immune system,” Knitz says. “They prevent autoimmune disease and put the brakes on the T cells when needed. However, in many tumors, Tregs are too numerous or overly suppressive, bringing the T cell response to a halt.”
Using medication that deactivates the Tregs can help boost the immune response in patients with cold tumors, the researchers found, as can radiation treatment that causes enough injury that the immune cells known as dendritic cells work to put the regular T cells into fight mode.
But this is only part of the story. The T cells need to know what to attack. “You need the radiation to create injury and bring in the immune cells so that the tumor can be recognized and targeted,” says Karam, also an associate professor of radiation oncology at the University of Colorado School of Medicine. “That way, the dendritic cells trigger the immune system to produce a lot of T cells, similar to what a vaccine does. Those T cells then go back to the tumor to kill cancer cells. The pieces are already in place; they just need the proper signals. Activating the dendritic cells is a crucial step in allowing radiation to heat up these cold tumors.”
Importantly, Karam and her team, which includes post-doctorate fellow Thomas Bickett, found that the radiation must be administered in a specific way.
“A specific dosing is needed,” Karam says. “You have to pulse it. You can’t just give one dose. You have to give it again and combine it with things that remove the suppression — the Tregs — while simultaneously keeping those antigen-presenting dendritic cells active and on board.”
Karam says the next step in her research is clinical trials she hopes will eventually change the treatment paradigm from surgery and weeks of chemotherapy and radiation to just three sessions of radiation and immunotherapy, then surgery. She is driven to change the standard of care for cold tumors, she explains, because of the horrendous effects they have on patients.
“These tumors resemble those in patients who are heavy smokers,” she says. “They’re very destructive to bone and muscle, infiltrating the tongue, jaw, gum, and lymph nodes. It’s horrible. We have very high failure rates with them, and the treatment often involves removing the tongue and weeks of radiation and chemotherapy, only for the patient to fail. I’m confident that we can do better for our patients.”

A multidisciplinary team of researchers from Duke-NUS Medical School and the Agency for Science, Technology and Research (A*STAR) in Singapore discovered a new mitochondrial peptide called MOCCI that plays an important role in regulating inflammation of blood vessel and immunity. The study, published in the journal Nature Communications, revealed how one gene encoded two molecules that provide two-pronged protection following viral infection.
Chronic and excessive inflammation of the blood vessels, known as vascular inflammation, can lead to tissue damage and cardiovascular diseases such as atherosclerosis and fibrosis. Although some therapies have shown promising results in clinical trials, they have considerable side effects, such as immunosuppression leading to increased risk of infection, and limited efficacy. Therefore, more effective treatments are urgently needed.
“In this study, we aimed to identify new targets to combat inflammation in the lining of blood vessels. Specifically, we wanted to target small naturally-produced peptides that have not been studied before,” explained Assistant Professor Lena Ho, from the Cardiovascular and Metabolic Diseases Programme at Duke-NUS, who led the team that included Associate Professor Ashley St John, Assistant Professor Owen Rackham and Senior Research Fellow Dr Cheryl Lee.
The Duke-NUS team, in collaboration with colleagues from the Institute of Molecular and Cell Biology at A*STAR Singapore, investigated a group of peptides called Mito-SEPs that localise in mitochondria, the cellular organelles well-known for their role in cellular energy production. After observing that Mito-SEPs appear to be involved in regulating inflammation, they screened cells from the lining of human aortic blood vessels to uncover peptides involved in this process.
They found a new peptide, which they named MOCCI — short for Modulator of Cytochrome C oxidase during Inflammation — that is made only when cells undergo inflammation and infection.
To their surprise, they discovered that MOCCI is a hitherto unknown component of Complex IV, a part of a series of enzymes in the mitochondria responsible for energy production, called the electron transport chain. During inflammation, MOCCI incorporates into Complex IV to dampen its activity. Collaborating with Assoc Prof St John at Duke-NUS, the researchers found that this dampening is required to reduce inflammation following viral infection.
“Our finding that the composition of the electron transport chain changes in response to inflammation is novel. MOCCI in essence repurposes part of the energy production centre in the cell to regulate inflammation,” said Dr Lee, the lead author of this study.
The researchers also discovered that MOCCI is made together with a micro-RNA molecule called miR-147b. The two molecules are made from different sections of the same gene. MOCCI originates from the sequence of the gene that codes for proteins, while miR-147b is made from the non-coding section.
While the miR-147b molecule also exerts anti-inflammatory effects, it actively prevents viruses from replicating at the same time. This implies that MOCCI and miR-147b function in tandem to help to control viral infection and suppress inflammation.
“This dual-pronged strategy is an elegant mechanism that the body has put in place to prevent excessive and potentially tissue-damaging inflammation during infection, such as the cytokine storm seen in COVID-19 infection, and colitis” said Asst Prof Ho. “The gene encoding MOCCI is one of the first genes described to have both coding and non-coding functions. The fact these dual functions are coordinated to achieve a concerted biological outcome is a significant finding in cell biology.”
Professor Patrick Casey, Senior Vice-Dean for Research at Duke-NUS, commented, “Medicine and healthcare advance with the aid of new discoveries in fundamental research. This study by Asst Prof Ho and her collaborators provides valuable insight on inflammation and immunity — a topic that has become even more important in the context of COVID-19.”
The researchers say the next step is to explore how to develop targeted pharmacological treatments that can mimic the anti-inflammatory effects of MOCCI and miR147b. They also plan to investigate the role of MOCCI in common chronic inflammatory diseases such as colitis and psoriasis.
Story Source:
Materials provided by Duke-NUS Medical School. Note: Content may be edited for style and length.

Researchers at Albert Einstein College of Medicine have designed an experimental drug that reversed key symptoms of Alzheimer’s disease in mice. The drug works by reinvigorating a cellular cleaning mechanism that gets rid of unwanted proteins by digesting and recycling them. The study was published online today in the journal Cell.
“Discoveries in mice don’t always translate to humans, especially in Alzheimer’s disease,” said co-study leader Ana Maria Cuervo, M.D., Ph.D., the Robert and Renée Belfer Chair for the Study of Neurodegenerative Diseases, professor of developmental and molecular biology, and co-director of the Institute for Aging Research at Einstein. “But we were encouraged to find in our study that the drop-off in cellular cleaning that contributes to Alzheimer’s in mice also occurs in people with the disease, suggesting that our drug may also work in humans.” In the 1990s, Dr. Cuervo discovered the existence of this cell-cleaning process, known as chaperone-mediated autophagy (CMA) and has published 200 papers on its role in health and disease.
CMA becomes less efficient as people age, increasing the risk that unwanted proteins will accumulate into insoluble clumps that damage cells. In fact, Alzheimer’s and all other neurodegenerative diseases are characterized by the presence of toxic protein aggregates in patients’ brains. The Cell paper reveals a dynamic interplay between CMA and Alzheimer’s disease, with loss of CMA in neurons contributing to Alzheimer’s and vice versa. The findings suggest that drugs for revving up CMA may offer hope for treating neurodegenerative diseases.
Establishing CMA’s Link to Alzheimer’s
Dr. Cuervo’s team first looked at whether impaired CMA contributes to Alzheimer’s. To do so, they genetically engineered a mouse to have excitatory brain neurons that lacked CMA. The absence of CMA in one type of brain cell was enough to cause short-term memory loss, impaired walking, and other problems often found in rodent models of Alzheimer’s disease. In addition, the absence of CMA profoundly disrupted proteostasis — the cells’ ability to regulate the proteins they contain. Normally soluble proteins had shifted to being insoluble and at risk for clumping into toxic aggregates.
Dr. Cuervo suspected the converse was also true: that early Alzheimer’s impairs CMA. So she and her colleagues studied a mouse model of early Alzheimer’s in which brain neurons were made to produce defective copies of the protein tau. Evidence indicates that abnormal copies of tau clump together to form neurofibrillary tangles that contribute to Alzheimer’s. The research team focused on CMA activity within neurons of the hippocampus — the brain region crucial for memory and learning. They found that CMA activity in those neurons was significantly reduced compared to control animals.