Breaking News
September 23, 2018 - an ancient art may work best to prevent falls in old age
September 23, 2018 - Consumption of foods with lower nutritional quality related to increased cancer risk
September 23, 2018 - Patient Health Information Often Shared Electronically
September 23, 2018 - Can machine learning bring more humanity to health care?
September 23, 2018 - Body organs undergo structural changes in response to diet
September 23, 2018 - Genetic polymorphisms linked with muscle injury and stiffness
September 23, 2018 - As states try to rein in drug spending, feds slap down one bold Medicaid move
September 22, 2018 - Why Eczema Is Tougher to Treat for Black Patients
September 22, 2018 - Team reveals that human genome could contain up to 20 percent fewer genes
September 22, 2018 - USC research uncovers previously unknown genetic risk factor for Alzheimer’s disease
September 22, 2018 - Novel method achieves accurate and precise temperature estimation in fat-containing tissues
September 22, 2018 - BSI accredits Oxehealth’s vital signs measurement software as Class IIa medical device
September 22, 2018 - Evolution of psychiatric disorders and human personality traits
September 22, 2018 - Obesity in early puberty doubles asthma risk for boy’s future offspring
September 22, 2018 - World’s most advanced real-time patient monitoring platform receives key US patent
September 22, 2018 - Study explores connection between sexuality and cognitive status in older adults
September 22, 2018 - LSTM partners with TB Alliance to develop novel TB drug regimens
September 22, 2018 - Annual wellness visits improve delivery of preventive services in elderly population
September 22, 2018 - CHMP provides positive opinion to Cabometyx for previously-treated patients with hepatocellular carcinoma
September 22, 2018 - Hispanic communities with high proportions of Hispanics face more cardiovascular-related death
September 22, 2018 - Vici syndrome – Genetics Home Reference
September 22, 2018 - Single-dose drug can shorten flu symptoms by about a day, studies suggest
September 22, 2018 - AMSBIO launches circulating tumor DNA Reference Standards
September 22, 2018 - Sandalwood mimicking odorant could stimulate hair growth in humans
September 22, 2018 - Overlooked immune cells could play a key role in cancer immunotherapy, claims new study
September 22, 2018 - Study reveals prevalence of diagnosed type 1 and type 2 diabetes among American adults
September 22, 2018 - Researchers develop fast detection strategy to know type of virus acquired by patients
September 22, 2018 - Global Prevalence of Insufficient Activity 27.5 Percent
September 22, 2018 - Strategies to protect bone health in hematologic stem cell transplant recipients
September 22, 2018 - Brigham Genomic Medicine program unravels 30 medical mysteries
September 22, 2018 - New system harnesses power of bubbles to destroy dangerous biofilms
September 22, 2018 - Inflammation plays crucial role in preventing heart attacks and strokes, study reveals
September 22, 2018 - Calorie dense, nutrient deficient meals common across the world
September 22, 2018 - Researchers develop technology to study behavior of implants without animal testing
September 22, 2018 - First gut bacteria in newborns may have lasting effect on ability to ward off chronic diseases
September 22, 2018 - Detection of BFD virus in parrots in 8 new countries raises concerns for threatened species
September 22, 2018 - Insulin treatment shows great potential against chronic bowel inflammation
September 22, 2018 - ‘Liking Gap’ Might Stand in Way of New Friendships
September 22, 2018 - Simple factors that can avoid harmful side effects in type 2 diabetes
September 22, 2018 - ALSAM Foundation invests additional $2 million for drug discovery and development projects
September 22, 2018 - Study findings may advance discussion of how to effectively curb human-wildlife conflict
September 22, 2018 - Dopamine neurons may involve in conditions ranging from Parkinson’s disease to schizophrenia
September 22, 2018 - Protein C and Protein S Tests: MedlinePlus Lab Test Information
September 22, 2018 - Obesity and diabetes—two reasons why we should be worried about the plastics that surround us
September 22, 2018 - Concern over fussy eating prompts parents to use non-responsive feeding practices
September 22, 2018 - Novel mathematical approach uncovers existence of unsuspected biological cycles
September 22, 2018 - Cancer Research UK invests £14 million to transform London into cancer biotherapeutics hub
September 22, 2018 - Scientists predict how well the body will fight lung cancer by analyzing immune cell shapes
September 22, 2018 - New outbreak of rare eye disease identified in contact lens wearers
September 22, 2018 - Iterum Initiates SURE 2 and SURE 3 Phase 3 Clinical Trials of IV and Oral Sulopenem in Complicated Urinary Tract and Complicated Intra-abdominal Infections
September 22, 2018 - Research finds divide in dental health accessibility between city and regional areas
September 22, 2018 - Premature babies show better brain development when fed breast milk, finds study
September 22, 2018 - Novel system uses AI to detect abnormalities in fetal hearts
September 22, 2018 - UNC scientists reveal new approach to prevent obesity and diabetes
September 22, 2018 - CWRU receives NIH grant to learn how non-coding genes contribute to spread of colorectal cancer
September 22, 2018 - Scientists better understand influenza virus and how it spreads
September 22, 2018 - Scientists to focus on length of time when a person is alive and healthy
September 22, 2018 - Study shows positive financial impacts of Medicaid expansion for low-income Michigan residents
September 22, 2018 - Innovative approach for developing vaccine against most prevalent human malaria parasite
September 22, 2018 - Decision aids for parents of children with minor head injuries help communicate with physicians
September 22, 2018 - Research scientist at Kessler Foundation receives $10,000 grant to study aphasia after stroke
September 22, 2018 - New findings on characteristics of Burning Mouth Syndrome
September 22, 2018 - Study sheds light on molecular mechanisms underlying progression of prion diseases
September 22, 2018 - Innovation Fund Denmark supports research project that aims to fight Clostridium difficile diarrhea
September 22, 2018 - Survey estimates caregiving costs for family members
September 22, 2018 - Inhibiting NF-kB improves heart function in a mouse model of Duchenne muscular dystrophy
September 22, 2018 - Introducing new EMR system may affect several aspects of clinic workflow
September 22, 2018 - Study finds why some human genes are more popular with biomedical researchers
September 22, 2018 - Finding epigenetic signature appears to predict inflammation risk in serious type of IBD
September 22, 2018 - Researchers develop light-based technique to measure very weak magnetic fields
September 22, 2018 - UAB researchers study dysfunction of the immune system associated with NSAID carprofen
September 22, 2018 - QIAGEN and DiaSorin launch automated, CE-marked workflow for high-throughput TB screening
September 22, 2018 - EFS checklist provides user-friendly tool for evaluating feeding skills in preterm infants
September 22, 2018 - Family history in blacks, Latinos associated with higher risk of AFib
September 22, 2018 - Researchers identify new genetic disorder in a human patient
September 22, 2018 - Cardiac MR With Contrast Feasible in Developing World
September 22, 2018 - Daily low-dose aspirin doesn’t reduce heart-attack risk in healthy people
September 21, 2018 - Children with asthma found to be disadvantaged in education and future occupation
September 21, 2018 - Interaction of chemical slurry and ancient shale in fracking wastewater causes radioactivity
September 21, 2018 - Scientists use mice to study transmission of Lyme disease bacteria by infected ticks
Researchers demonstrate new strategy for stimulating autophagy

Researchers demonstrate new strategy for stimulating autophagy

image_pdfDownload PDFimage_print

Brown University researchers studying the biology of aging have demonstrated a new strategy for stimulating autophagy, the process by which cells rebuild themselves by recycling their own worn-out parts.

In a study published in the journal Cell Reports, the researchers show that the approach increased the lifespans of worms and flies, and experiments in human cells hint that the strategy could be useful in future treatments for Alzheimer’s disease, ALS and other age-related neurodegenerative conditions.

“Autophagy dysfunction is present across a range of age-related diseases including neurodegeneration,” said Louis Lapierre, an assistant professor of molecular biology, cell biology and biochemistry at Brown who led the work. “We and others think that by learning how to influence this process pharmacologically, we might be able to affect the progression of these diseases. What we’ve shown here is a new and conserved entry point for stimulating autophagy.”

Autophagy has become a hot topic in recent years, earning its discoverer the Nobel Prize in Physiology and Medicine in 2016. The process involves the rounding up of misfolded proteins and obsolete organelles within a cell into vesicles called autophagosomes. The autophagosomes then fuse with a lysosome, an enzyme-containing organelle that breaks down those cellular macromolecules and converts it into components the cell can re-use.

Lapierre and his colleagues wanted to see if they could increase autophagy by manipulating a transcription factor (a protein that turns gene expression on and off) that regulates autophagic activity. In order for the transcription factor to switch autophagic activity on, it needs to be localized in the nucleus of a cell. So Lapierre and his team screened for genes that enhance the level of the autophagy transcription factor, known as TFEB, within nuclei.

Using the nematode C. elegans, the screen found that reducing the expression of a protein called XPO1, which transports proteins out of the nucleus, leads to nuclear accumulation of the nematode version of TFEB. That accumulation was associated with an increase in markers of autophagy, including increased autophagosome, autolysosomes as well as increased lysosome biogenesis. There was also a marked increase in lifespan among the treated nematodes of between about 15 and 45 percent.

“What we showed was that by blocking the escape of this transcription factor from the nucleus, we could not only influence autophagy but we could get an increase in lifespan as well,” Lapierre said.

The next step was to see if there were drugs that could mimic the effect of the gene inhibition used in the screening experiment. The researchers found that selective inhibitors of nuclear export (SINE), originally developed to inhibit XPO1 to treat cancers, had a similar effect — increasing markers of autophagy and significantly increasing lifespan in nematodes.

The researchers then tested SINE on a genetically modified fruit fly that serves as a model organism for the neurodegenerative disease ALS. Those experiments showed a small but significant increase in the lifespans of the treated flies. “Our data suggests that these compounds can alleviate some of the neurodegeneration in these flies,” Lapierre said.

As a final step, the researchers set out to see if XPO1 inhibition had similar effects on autophagy in human cells as it had in the nematodes. After treating a culture of human HeLa cells with SINE, the researchers found that, indeed, TFEB concentrations in nuclei increased, as did markers of autophagic activity and lysosomal biogenesis.

“Our study tells us that the regulation of the intracellular partitioning of TFEB is conserved from nematodes to humans and that SINE could stimulate autophagy in humans,” Lapierre said. “SINE have been recently shown in clinical trials for cancer to be tolerated, so the potential for using SINE to treat other age-related diseases is there.”

Future research, Lapierre said, will focus on testing these drugs in more clinically relevant models of neurodegenerative diseases. But this initial research is a proof of concept for this strategy as a means to increase autophagy and potentially treat age-related diseases.

Lapierre is a faculty member in the newly approved Center on the Biology of Aging within the Brown Institute for Translational Science. This center, led by Professor of Biology John Sedivy, studies the biological mechanisms of aging. The center’s mission is to expand biomedical research and education programs in the emerging discipline of biogerontology, and to bring forth scientific discoveries related to aging and associated disorders.

Source:

https://news.brown.edu/articles/2018/05/autophagy

Tagged with:

About author

Related Articles