Nav: Home

Discovery identifies new RX target for age-rleated macular degeneration & Alzheimer's

March 07, 2016

New Orleans, LA - For the first time, researchers at LSU Health New Orleans have shown that a protein critical to the body's ability to remove waste products from the brain and retina is diminished in age-related macular degeneration (AMD), after first making the discovery in an Alzheimer's disease (AD) brain. The research team, led by Walter Lukiw, PhD, Professor of Neurology, Neuroscience and Ophthalmology at LSU Health New Orleans Neuroscience Center, also discovered a key reason, identifying a new treatment target. The paper, microRNA-34a-mediated down-regulation of the microglial-enriched triggering receptor and phagocytosis-sensor TREM2 in age-related macular degeneration, was published March 7, 2016, online at http://dx.plos.org/10.1371/journal.pone.0150211 in the journal, PLOS ONE.

During their normal day-to-day operation, the brain and retina produce relatively large quantities of waste products, which have to be cleared away so that they do not clog up the delicate parts of the thinking and visual system. Part of the waste disposal system consists of a very special waste-sensing transmembrane protein located in highly specialized cells called microglial cells found in the brain and retina. This waste-sensing protein in microglial cells is known to scientists as the "triggering receptor expressed in microglia," or TREM2 protein.

In this work, the researchers examined human AD-affected brain and AMD-affected retina, the retina of aging 5xFAD transgenic animals and microglial and other brain and retinal cells in culture.

"We have discovered that in age-related degenerative diseases of the brain, such as Alzheimer's disease, and the retina, such as age-related macular degeneration, there is a lowered and insufficient amount of TREM2 protein, and this may be in part responsible for the inability of the brain and retina to clear away their end-stage waste products," notes Dr. Lukiw, who is also the Bollinger Professor of Alzheimer's Disease at LSU Health New Orleans.

These waste products consist chiefly of amyloid -- misfolded proteins, small various remnants of the innate immune system, small, very sticky toxic proteins and prominently, a 42-amino acid amyloid protein called Aβ42 peptide. Because they cannot be properly removed, the waste products accumulate in the brain and retina and contribute to the progressive appearance of insoluble lesions called senile plaques in the brain and drusen in the retina. These lesions ultimately contribute to episodes of age-related inflammatory degeneration.

"We have also discovered that an excessive amount of a small piece of ribonucleic acid (RNA) called microRNA-34a, or miRNA-34a, is in part responsible for insufficient TREM2 protein," adds Dr. Lukiw. "These scientific findings further indicate that getting rid of the excessive miRNA-34a to restore normal TREM2 abundance may provide a highly effective therapeutic strategy for the treatment of both degenerative diseases of the brain, such as Alzheimer's disease, and progressive diseases of the retina, such as age-related macular degeneration."
-end-
The LSU Health New Orleans and Ruston, LA research teams also included Drs. Surjyadipta Bhattacharjee, Yuhai Zhao and Prerna Dua, as well as Dr. Evgeny I. Rogaev at the University of Massachusetts and Moscow State University.

This research was supported by grants from the National Institutes of Health (NIH) National Eye Institute (NEI), the National Institute on Aging (NIA), Research to Prevent Blindness (RPB), the Louisiana Biotechnology Research Network (LBRN), the Russian Academy of Sciences and the Russian Science Foundation (RAS/RSF).

LSU Health Sciences Center New Orleans educates Louisiana's health care professionals. The state's health sciences university leader, LSU Health New Orleans includes a School of Medicine, the state's only School of Dentistry, Louisiana's only public School of Public Health, and Schools of Allied Health Professions, Nursing, and Graduate Studies. LSU Health New Orleans faculty take care of patients in public and private hospitals and clinics throughout the region. In the vanguard of biosciences research in a number of areas in a worldwide arena, the LSU Health New Orleans research enterprise generates jobs and enormous economic impact. Faculty have made lifesaving discoveries and continue to work to prevent, advance treatment, or cure disease. To learn more, visit http://www.lsuhsc.edu, http://www.twitter.com/LSUHealthNO or http://www.facebook.com/LSUHSC.

Louisiana State University Health Sciences Center

Related Brain Articles:

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.
Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.
BRAIN Initiative tool may transform how scientists study brain structure and function
Researchers have developed a high-tech support system that can keep a large mammalian brain from rapidly decomposing in the hours after death, enabling study of certain molecular and cellular functions.
Wiring diagram of the brain provides a clearer picture of brain scan data
In a study published today in the journal BRAIN, neuroscientists led by Michael D.
Blue Brain Project releases first-ever digital 3D brain cell atlas
The Blue Brain Cell Atlas is like ''going from hand-drawn maps to Google Earth'' -- providing previously unavailable information on major cell types, numbers and positions in all 737 brain regions.
Landmark study reveals no benefit to costly and risky brain cooling after brain injury
A landmark study, led by Monash University researchers, has definitively found that the practice of cooling the body and brain in patients who have recently received a severe traumatic brain injury, has no impact on the patient's long-term outcome.
Brain cells called astrocytes have unexpected role in brain 'plasticity'
Researchers from the Salk Institute have shown that astrocytes -- long-overlooked supportive cells in the brain -- help to enable the brain's plasticity, a new role for astrocytes that was not previously known.
Largest brain study of 62,454 scans identifies drivers of brain aging
In the largest known brain imaging study, scientists from Amen Clinics (Costa Mesa, CA), Google, John's Hopkins University, University of California, Los Angeles and the University of California, San Francisco evaluated 62,454 brain SPECT (single photon emission computed tomography) scans of more than 30,000 individuals from 9 months old to 105 years of age to investigate factors that accelerate brain aging.
Is whole-brain radiation still best for brain metastases from small-cell lung cancer?
University of Colorado Cancer Center study compares outcomes of 5,752 small-cell lung cancer patients who received whole-brain radiation therapy (WBRT) with those of 200 patients who received stereotactic radiosurgery (SRS), finding that the median overall survival was actually longer with SRS (10.8 months with SRS versus 7.1 months with WBRT).
Atlas of brain blood vessels provides fresh clues to brain diseases
Even though diseases of the brain vasculature are some of the most common causes of death in the West, knowledge of these blood vessels is limited.
More Brain News and Brain Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.