Breaking News
January 18, 2019 - New study shows link between secondhand smoke and cardiac arrhythmia
January 18, 2019 - DZIF scientists reveal problems with available diagnostics for Zika and chikungunya virus
January 18, 2019 - Breast cancers more likely to metastasize in young women within 10 years of giving birth
January 18, 2019 - Blood vessels can now be created perfectly in a petri dish
January 18, 2019 - Study identifies prominent socioeconomic and racial disparities in health behavior in Indiana
January 18, 2019 - Young-Onset Type 2 Diabetes Tied to Increased Hospitalization Risk
January 18, 2019 - For-profit nursing schools associated with lower performance on nurse licensure test
January 18, 2019 - Considering the culture of consent in medicine
January 18, 2019 - Researchers identify comprehensive guidelines for managing severe atopic dermatitis
January 18, 2019 - Analyzing proteins in blister fluid may classify burn severity more accurately
January 18, 2019 - Study finds higher suicide rates among youth who were Medicaid enrollees
January 18, 2019 - Opioid drugs often overprescribed to children for pain relief, say CHOP surgeons
January 18, 2019 - New biodegradable wound dressing material accelerates healing
January 18, 2019 - Life in Space May Take Toll on Spinal Muscles
January 18, 2019 - Bulldogs’ screw tails linked to human genetic disease
January 18, 2019 - Immunotherapy target identified for pediatric cancers
January 18, 2019 - Financial stress may increase heart disease risk in African Americans
January 18, 2019 - Scientists solve another piece of Ebola virus puzzle
January 18, 2019 - New project finds how endocrine disruptors interfere with thyroid functions
January 18, 2019 - Research finds decline in ketone body utilization when coronary circulation is reduced
January 18, 2019 - Let’s map our DNA and save billions each year in health costs
January 18, 2019 - AI demonstrates potential to identify irregular heart rhythms as well as humans
January 17, 2019 - Study shows link between air pollution and increased risk of sleep apnea
January 17, 2019 - Neck-strengthening exercises can protect athletes from concussions
January 17, 2019 - Computer model shows how to better control MRSA outbreaks
January 17, 2019 - Pain is unpleasant, and now scientists have identified the set of responsible neurons
January 17, 2019 - CUIMC Celebrates 2018-2019
January 17, 2019 - Study reveals potential pathway for endothelial cells to avoid apoptosis
January 17, 2019 - Hamilton Storage launches LabElite DeCapper SL to expand LabElite product family
January 17, 2019 - Location of epigenetic changes co-locate with genetic signal causing psychartric disorder
January 17, 2019 - Researchers awarded 6.1 million euros to address female fertility problems
January 17, 2019 - Counseling appointments fail to reduce weight gain during pregnancy, shows study
January 17, 2019 - Contraceptive patch that could provide 6 months of contraception within seconds
January 17, 2019 - Yeast model may pave way for development of novel therapies for metabolic disorders
January 17, 2019 - Study determines impact of antibiotic perturbation of the gut microbiome on skeletal health
January 17, 2019 - Cardiometabolic Risk Up With Tourette, Chronic Tic Disorder
January 17, 2019 - Hong Kong scientists claim ‘broad-spectrum’ antiviral breakthrough
January 17, 2019 - Researchers discover the brain cells that make pain unpleasant | News Center
January 17, 2019 - Hepatitis Is Common in New Cancer Patients
January 17, 2019 - Podcast: KHN’s ‘What The Health?’ Drug Prices Are Rising Again. Is Someone Going To Do Something About It?
January 17, 2019 - Smoking significantly increases your biological age, study shows
January 17, 2019 - B-group vitamins may be beneficial for people with first episode psychosis
January 17, 2019 - Researchers demonstrate how manganese produces parkinsonian syndrome
January 17, 2019 - Researchers suggest link between personality type and attitude towards others’ bodies
January 17, 2019 - Mutant mice administered with cocaine failed to exhibit hyperactivity, shows study
January 17, 2019 - Health Tip: Understanding a Heart Murmur
January 17, 2019 - Gut protein mutations shield against spikes in glucose
January 17, 2019 - Engineered immune cells target broad range of pediatric solid tumors in mice | News Center
January 17, 2019 - Study provides comprehensive description of associations between mental disorders
January 17, 2019 - Study finds link between high pesticide exposure and poor sense of smell among farmers
January 17, 2019 - Many cancer patients have undiagnosed hepatitis
January 17, 2019 - New study finds only 13% of outpatient antibiotic prescriptions to be appropriate
January 17, 2019 - Stem cell-based approach to diabetes offers hope for treatment
January 17, 2019 - New project receives €8.65 million from EU and Canada to ease genomic, health data sharing
January 17, 2019 - Improvements in pharmacological study to fight cognitive impairment in schizophrenia
January 17, 2019 - Study looks at trends over time in oral antibiotic prescribing by dermatologists
January 17, 2019 - Most substance use disorder treatment facilities do not offer medication treatment
January 17, 2019 - Multiple sclerosis could benefit from stem cell therapy
January 17, 2019 - Researchers manipulate T cells to improve transplant success
January 17, 2019 - Put away your rulers and reach for your phone
January 17, 2019 - Mindfulness linked with fewer menopausal symptoms
January 17, 2019 - Integrated care to women with PMADs offered at several levels
January 17, 2019 - Researchers identify MANF as a rejuvenating factor in parabiosis
January 17, 2019 - Truncal mutations study suggests new direction in origins of cancer
January 17, 2019 - Beckman Coulter launches new ClearLLab 10C System for clinical flow cytometry lab
January 17, 2019 - Effects of linoleic acid on the body are largely dependent on genes, shows study
January 17, 2019 - Pre-injury exercise reduces damage to both muscles and nerves, study finds
January 17, 2019 - Minimizing Antibody Size to Maximize Research Potential
January 17, 2019 - Research finds large genome in tiny forest defoliator
January 17, 2019 - Technology helps reduce the yearning for unhealthy food
January 17, 2019 - Imec develops prototype cardiovascular device
January 17, 2019 - New Drug Application for Insomnia Disorder Treatment Lemborexant Submitted in the United States
January 17, 2019 - What you should know about teeth whitening
January 17, 2019 - Why Older Adults Should Eat More Protein (And Not Overdo Protein Shakes)
January 17, 2019 - Colorectal cancer mortality rates predicted to increase globally
January 17, 2019 - Scientists discover mutational signatures of tumor hypoxia
January 17, 2019 - New evidence shows how fever alters immune cells
January 17, 2019 - Researchers find new class of blood pressure-regulating peptides in vampire bat venom
January 17, 2019 - Promega to exhibit new Maxwell RSC48 platform at 2019 Festival of Genomics
January 17, 2019 - Study pinpoints immune cells that could be key to tackling hypertension
Targeting immune checkpoints in microglia could reduce out-of-control neuroinflammation

Targeting immune checkpoints in microglia could reduce out-of-control neuroinflammation

image_pdfDownload PDFimage_print

A group of Massachusetts General Hospital (MGH) investigators is proposing that targeting immune checkpoints – molecules that regulate the activity of the immune system – in immune cells called microglia could reduce the inflammatory aspects of important neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS). In their review article published in the October issue of Nature Neuroscience, they discuss how uncontrolled activity of microglia contributes to neurodegeneration in these and other neurodegenerative conditions.

“Microglia have three essential functions: a ‘sentinel’ function that surveys and senses changes within the brain, a ‘nurturer’ function that promotes neuronal wellbeing through actions such as removing dying cells and debris, and a ‘warrior’ function that defends the brain against infections and toxins,” explains Joseph El Khoury, MD , of the MGH Center for Immunology and Inflammatory Diseases and the Division of Infectious Diseases, senior author of the report. “In healthy brains, immune checkpoints in microglia keep the ‘warrior’ function in check. Disruption of those checkpoints initiates or propagates neurodegeneration.”

While microglia have long been recognized as the innate immune cells of the brain, the MGH team is the first to delineate these three functions, based on patterns of gene expression within the cells. After detailing how microglia carry out these functions, the authors review how the processes can go awry in several neurodegenerative disorders:

  • In Alzheimer’s disease, microglia are known to accumulate around amyloid-beta plaques, and mutations in several microglial genes can increase the risk of developing the disease. An inability of microglia to keep up with persistent production of amyloid-beta leads to the release of inflammatory factors that further compromise the cells’ ‘nurturer’ functions, eventually transforming them into a disease-associated form that induces persistent, damaging neuroinflammation;
  • In Parkinson’s disease, activated microglia are known to be abundant in the substantia nigra, the brain structure that is damaged in the disease. PET studies have shown widespread inflammatory microglia early in the course of the disease, and evidence suggests that the same sort of ‘double-edged sword’ situation seen in Alzheimer’s disease – in which initially protective microglia escape regulation, leading to persistent damaging neuroinflammation – also occurs in Parkinson’s.
  • In ALS, inflammatory microglia have been found near injured neurons in the brain of patients. In a mouse model carrying a mutant SOD1 gene – one of several genes that, when mutated, can cause inherited forms of ALS – microglia have been found to be protective at disease onset but neurotoxic at later stages.

The investigators also describe how initially protective microglia can escape regulation and become damaging in multiple sclerosis, Huntington’s disease, and several other neurodegenerative conditions.

The team identifies three potential immune checkpoints in microglia – Trem2, which regulates all three functions; Cx3cr1, which regulates the sentinel and nurturer functions, and the progranulin pathway, which also regulates sentinel and nurturer functions. Evidence points to dysregulation of both Trem2 and progranulin in Alzheimer’s disease, ALS and other disorders; and Cx3cr1 is known to alter the course of disease in animal models of Alzheimer’s disease, Parkinson’s disease, ALS and other disorders.

While immune checkpoint therapies for cancer – discovery of which recently received the Nobel Prize in Medicine – are designed to inhibit checkpoints that prevent the immune system from attacking tumor cells, in neurodegenerative disease the goal would be to activate checkpoints that could reduce and potentially eliminate out-of-control neuroinflammation, returning microglia to their healthy neuroprotective state. El Khoury and his colleagues are now working to improve understanding of how microglia contribute to neurodegeneration.

“Analyzing patterns of microglial gene transcription and regulation in several disease states, understanding how those patterns may be altered by aging and disease progression, and correlating those changes to microglial behavior is essential,” he says. “Expanding studies from animal models to human patients remains a challenge that will require development of new, reliable cellular models based on patient samples and additional technologies for imaging and analysis. And new techniques to incorporate microglia into three-dimensional organoids – miniature organs grown from living tissues – are a crucial next breakthrough that needs to be achieved.” El Khoury is an associate professor of Medicine at Harvard Medical School.

Source:

https://www.massgeneral.org/about/pressrelease.aspx?id=2306

Tagged with:

About author

Related Articles